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Abrantes AM, Pires AS, Monteiro L, Teixo R, Neves AR, Tavares NT, Marques IA, Botelho MF. Tumour functional imaging by PET. Biochim Biophys Acta Mol Basis Dis 2020; 1866:165717. [PMID: 32035103 DOI: 10.1016/j.bbadis.2020.165717] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 01/15/2020] [Accepted: 01/30/2020] [Indexed: 12/18/2022]
Abstract
Carcinogenesis is a complex multistep process, characterized by changes at different levels, both genetic and epigenetic, which alter cell metabolism. Positron emission tomography (PET) is a very sensitive image modality that allows to evaluate oncometabolism. PET functionalities are immense, since by labelling a molecule that specifically intervenes in a biochemical regulatory pathway of interest with a positron-emitting radionuclide, we can easily image that pathway. Thus, PET makes possible imaging several metabolic processes and assessing risk prediction, screening, diagnosis, response to therapy, metastization and recurrence. In this paper, we provide an overview of different radiopharmaceuticals developed for PET use in oncology, with a focus on brain tumours, breast cancer, hepatocellular carcinoma, neuroendocrine tumours, bladder cancer and prostate cancer because for these cancer types PET has been shown to be valuable. Most of the described tracers are just used in the research environment, with the aim to assess if these tracers could be able to offer an improvement concerning staging/restaging, characterization and stratification of different types of cancer, as well as therapeutic response assessment. In pursuit of personalized therapy, we briefly discuss the more established metabolic tracers and describe recent work on the development of new radiopharmaceuticals, aware that there will continue to exist diagnostic challenges to face modern cancer medicine.
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Affiliation(s)
- Ana Margarida Abrantes
- Biophysics Institute, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Clinical Academic Center of Coimbra, 3004-561 Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; CNC.IBILI Consortium/Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal.
| | - Ana Salomé Pires
- Biophysics Institute, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Clinical Academic Center of Coimbra, 3004-561 Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; CNC.IBILI Consortium/Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal.
| | - Lúcia Monteiro
- Biophysics Institute, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Clinical Academic Center of Coimbra, 3004-561 Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Ricardo Teixo
- Biophysics Institute, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Clinical Academic Center of Coimbra, 3004-561 Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; CNC.IBILI Consortium/Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal
| | - Ana Rita Neves
- Biophysics Institute, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Clinical Academic Center of Coimbra, 3004-561 Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Project Development Office, Department of Mathematics and Computer Science, Eindhoven University of Technology (TU/e), NL-5612 AE Eindhoven, the Netherlands
| | - Nuno Tiago Tavares
- Biophysics Institute, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Clinical Academic Center of Coimbra, 3004-561 Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Inês Alexandra Marques
- Biophysics Institute, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Clinical Academic Center of Coimbra, 3004-561 Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; CNC.IBILI Consortium/Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Maria Filomena Botelho
- Biophysics Institute, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Clinical Academic Center of Coimbra, 3004-561 Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; CNC.IBILI Consortium/Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal.
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Grkovski M, Gharzeddine K, Sawan P, Schöder H, Michaud L, Weber WA, Humm JL. 11C-Choline Pharmacokinetics in Recurrent Prostate Cancer. J Nucl Med 2018; 59:1672-1678. [PMID: 29626123 PMCID: PMC6225540 DOI: 10.2967/jnumed.118.210088] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Accepted: 03/23/2018] [Indexed: 11/16/2022] Open
Abstract
The aim of this study was to investigate the value of pharmacokinetic modeling for quantifying 11C-choline uptake in patients with recurrent prostate cancer. Methods: In total, 194 patients with clinically suspected recurrence of prostate cancer underwent 11C-choline dynamic PET over the pelvic region (0-8 min), followed by a 6-min static acquisition at about 25 min after injection. Regions of interest were drawn over sites of disease identified by a radiologist with experience in nuclear medicine. 11C-choline uptake and pharmacokinetics were evaluated by SUV, graphical analysis (Patlak plot; KiP), and 1- and 2-compartment pharmacokinetic models (K1, K1/k2, k3, k4, and the macro parameter KiC). Twenty-four local recurrences, 65 metastatic lymph nodes, 19 osseous metastases, and 60 inflammatory lymph nodes were included in the analysis, which was subsequently repeated for regions of interest placed over the gluteus maximus muscle and adipose tissue as a control. Results: SUVmean and KiP were 3.60 ± 2.16 and 0.28 ± 0.22 min-1 in lesions, compared with 2.11 ± 1.33 and 0.15 ± 0.10 min-1 in muscle and 0.26 ± 0.07 and 0.02 ± 0.01 min-1 in adipose tissue. According to the Akaike information criterion, the 2-compartment irreversible model was most appropriate in 85% of lesions and resulted in a K1 of 0.79 ± 0.98 min-1 (range, 0.11-7.17 min-1), a K1/k2 of 2.92 ± 3.52 (range, 0.31-20.00), a k3 of 0.36 ± 0.30 min-1 (range, 0.00-1.00 min-1) and a KiC of 0.28 ± 0.22 min-1 (range, 0.00-1.33 min-1). The Spearman ρ between SUV and KiP, between SUV and KiC, and between KiP and KiC was 0.94, 0.91, and 0.97, respectively, and that between SUV and K1, between SUV and K1/k2, and between SUV and k3 was 0.70, 0.44, and 0.33, respectively. Malignant lymph nodes exhibited a higher SUV, KiP, and KiC than benign lymph nodes. Conclusion: Although 11C-choline pharmacokinetic modeling has potential to uncouple the contributions of different processes leading to intracellular entrapment of 11C-choline, the high correlation between SUV and both KiP and KiC supports the use of simpler SUV methods to evaluate changes in 11C-choline uptake and metabolism for treatment monitoring.
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Affiliation(s)
- Milan Grkovski
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Karem Gharzeddine
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Peter Sawan
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Heiko Schöder
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
- Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, New York; and
| | - Laure Michaud
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Wolfgang A Weber
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
- Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, New York; and
- University Hospital Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - John L Humm
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York
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Schwarzenböck SM, Schmeja P, Kurth J, Souvatzoglou M, Nawroth R, Treiber U, Kundt G, Berndt S, Graham K, Senekowitsch-Schmidtke R, Schwaiger M, Ziegler SI, Dinkelborg L, Wester HJ, Krause BJ. Comparison of [(11)C]Choline ([(11)C]CHO) and [(18)F]Bombesin (BAY 86-4367) as Imaging Probes for Prostate Cancer in a PC-3 Prostate Cancer Xenograft Model. Mol Imaging Biol 2017; 18:393-401. [PMID: 26483088 DOI: 10.1007/s11307-015-0901-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE Carbon-11- and fluorine-18-labeled choline derivatives are commonly used in prostate cancer imaging in the clinical setting for staging and re-staging of prostate cancer. Due to a limited detection rate of established positron emission tomography (PET) tracers, there is a clinical need for innovative tumor-specific PET compounds addressing new imaging targets. The aim of this study was to compare the properties of [(18)F]Bombesin (BAY 86-4367) as an innovative biomarker for prostate cancer imaging targeting the gastrin-releasing peptide receptor and [(11)C]Choline ([(11)C]CHO) in a human prostate tumor mouse xenograft model by small animal PET/X-ray computed tomography (CT). PROCEDURES We carried out a dual-tracer small animal PET/CT study comparing [(18)F]Bombesin and [(11)C]CHO. The androgen-independent human prostate tumor cell line PC-3 was implanted subcutaneously in the flanks of nu/nu NMRI mice (n = 10) (PET/CT measurements of two [(11)C]Choline mice could not be analyzed due to technical reasons). [(18)F]Bombesin and [(11)C]CHO PET/CT imaging was performed about 3-4 weeks after the implantation of PC-3 cells on two separate days. After the intravenous tail vein injection of 14 MBq [(18)F]Bombesin and 37 MBq [(11)C]CHO, respectively, a dynamic study over 60 min was acquired in list mode using an Inveon animal PET/CT scanner (Siemens Medical Solutions). The sequence of [(18)F]Bombesin and [(11)C]CHO was randomized. Image analysis was performed using summed images as well as dynamic data. To calculate static and dynamic tumor-to-muscle (T/M), tumor-to-blood (T/B), liver-to-blood (L/B), and kidney-to-blood (K/B) ratios, 4 × 4 × 4 mm(3) volumes of interest (VOIs) of tumor, muscle (thigh), liver, kidney, and blood derived from transversal slices were used. RESULTS The mean T/M ratio of [(18)F]Bombesin and [(11)C]CHO was 6.54 ± 2.49 and 1.35 ± 0.30, respectively. The mean T/B ratio was 1.83 ± 0.79 for [(18)F]Bombesin and 0.55 ± 0.10 for [(11)C]CHO. The T/M ratio as well as the T/B ratio for [(18)F]Bombesin were significantly higher compared to those for [(11)C]CHO (p < 0.001, respectively). Kidney and liver uptake was statistically significantly lower for [(18)F]Bombesin (K/B 3.41 ± 0.81, L/B 1.99 ± 0.38) compared to [(11)C]CHO [K/B 7.91 ± 1.85 (p < 0.001), L/B 6.27 ± 1.99 (p < 0.001)]. The magnitudes of the time course of T/M and T/B ratios (T/M and T/Bdyn ratios) were statistically significantly different (showing a higher uptake of [(18)F]Bombesin compared to [(11)C]CHO); additionally, also the change of the T/M and T/B ratios over time was significantly different between both tracers in the dynamic analysis (p < 0.001, respectively). Furthermore, there was a statistically significantly different change of the K/B and L/B ratios over time between the two tracers in the dynamic analysis (p = 0.026 and p < 0.001, respectively). CONCLUSIONS [(18)F]Bombesin (BAY 86-4367) visually and semi-quantitatively outperforms [(11)C]CHO in the PC-3 prostate cancer xenograft model. [(18)F]Bombesin tumor uptake was significantly higher compared to [(11)C]CHO. [(18)F]Bombesin showed better imaging properties compared to the clinically utilized [(11)C]CHO due to a higher tumor uptake as well as a lower liver and kidney uptake.
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Affiliation(s)
- Sarah Marie Schwarzenböck
- Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. .,Department of Nuclear Medicine, Rostock University Medical Centre, Gertrudenplatz 1, 18057, Rostock, Germany.
| | - Philipp Schmeja
- Department of Nuclear Medicine, Rostock University Medical Centre, Gertrudenplatz 1, 18057, Rostock, Germany
| | - Jens Kurth
- Department of Nuclear Medicine, Rostock University Medical Centre, Gertrudenplatz 1, 18057, Rostock, Germany
| | - Michael Souvatzoglou
- Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany.,Department of Nuclear Medicine, Ulm University, Albert-Einstein-Allee 23, 89081, Ulm, Germany
| | - Roman Nawroth
- Department of Urology, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany
| | - Uwe Treiber
- Department of Urology, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany
| | - Guenther Kundt
- Department of Biostatistics and Informatics, Rostock University Medical Centre, Ernst-Heydemann-Str. 8, 18057, Rostock, Germany
| | - Sandra Berndt
- Global Drug Discovery, Bayer Healthcare, Muellerstr. 178, 13353, Berlin, Germany
| | - Keith Graham
- Global Drug Discovery, Bayer Healthcare, Muellerstr. 178, 13353, Berlin, Germany
| | - Reingard Senekowitsch-Schmidtke
- Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany
| | - Markus Schwaiger
- Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany
| | - Sibylle I Ziegler
- Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany
| | | | - Hans-Jürgen Wester
- Institution of Pharmaceutical Radiochemistry, Technische Universität München, Walther-Meißner-Str. 3, 85748, Garching, Germany
| | - Bernd Joachim Krause
- Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany.,Department of Nuclear Medicine, Rostock University Medical Centre, Gertrudenplatz 1, 18057, Rostock, Germany
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Singh A, Kulkarni HR, Baum RP. Imaging of Prostate Cancer Using 64 Cu-Labeled Prostate-Specific Membrane Antigen Ligand. PET Clin 2017; 12:193-203. [DOI: 10.1016/j.cpet.2016.12.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Zhang Q, Chen S, Zeng L, Chen Y, Lian G, Qian C, Li J, Xie R, Huang KH. New developments in the early diagnosis of pancreatic cancer. Expert Rev Gastroenterol Hepatol 2017; 11:149-156. [PMID: 27937041 DOI: 10.1080/17474124.2017.1271323] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Pancreatic cancer is an aggressive carcinoma of the digestive system and radical resection, which is available to very few patients, is the only possibility for cure. Since therapeutic choices are limited at the advanced stage, screening and early diagnostic tools are indispensable for a better prognosis. Areas covered: This review illustrates serologic and imaging examinations, and carbohydrate antigens, microRNAs, methylation biomarkers, molecules in exosomes, ultrasound, computed tomography, magnetic resonance imaging, positron emission tomography and endoscopic retrograde cholangiopancreatography, among other topics. No matter which approach is used, the accuracy of early diagnosis is extremely low. Combining different methods greatly improves the accuracy of early diagnosis. This review was conducted utilizing PubMed with key search words pancreatic cancer, early diagnosis, biomarkers and imaging. Expert commentary: Appropriate combination of biomarkers and imaging technologies will become standard practice in the future. Because the incidence of and mortality from pancreatic cancer is rising, further study of new approaches for the early detection of pancreatic tumors is essential.
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Affiliation(s)
- QiuBo Zhang
- a Department of Gastroenterology , Lihuili Hospital of Ningbo Medical Center , Ningbo , China
| | - ShaoJie Chen
- b Department of Oncology , the Fifth Affiliated Hospital of Sun Yat-Sen University , Zhuhai , China
| | - LinJuan Zeng
- b Department of Oncology , the Fifth Affiliated Hospital of Sun Yat-Sen University , Zhuhai , China
| | - YinTing Chen
- c Department of Gastroenterology , Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University , Guangzhou , China
| | - GuoDa Lian
- c Department of Gastroenterology , Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University , Guangzhou , China
| | - ChenChen Qian
- c Department of Gastroenterology , Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University , Guangzhou , China
| | - JiaJia Li
- c Department of Gastroenterology , Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University , Guangzhou , China
| | - RuiJie Xie
- c Department of Gastroenterology , Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University , Guangzhou , China
| | - Kai-Hong Huang
- c Department of Gastroenterology , Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University , Guangzhou , China
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Schwarzenböck SM, Gertz J, Souvatzoglou M, Kurth J, Sachs D, Nawroth R, Treiber U, Schuster T, Senekowitsch-Schmidtke R, Schwaiger M, Ziegler SI, Henriksen G, Wester HJ, Krause BJ. Comparison of [¹¹C]choline ([¹¹C]CHO) and S(+)-β-methyl-[¹¹C]choline ([¹¹C]SMC) as imaging probes for prostate cancer in a PC-3 prostate cancer xenograft model. Mol Imaging Biol 2015; 17:248-56. [PMID: 25163420 DOI: 10.1007/s11307-014-0782-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE Carbon-11- and fluorine-18-labeled choline derivatives have been introduced as promising tracers for prostate cancer imaging. However, due to limited specificity and sensitivity, there is a need for new tracers with higher sensitivity and specificity for diagnosing prostate cancer to improve tracer uptake and enhance imaging contrast. The aim of this study was to compare the properties of [(11)C]choline ([(11)C]CHO) with S(+)-β-methyl-[(11)C]choline ([(11)C]SMC) as tracer for prostate cancer imaging in a human prostate tumor mouse xenograft model by small-animal positron emission tomography/X-ray computed tomography (PET/CT). PROCEDURES We carried out a dual-tracer small-animal PET/CT study comparing [(11)C]CHO and [(11)C]SMC. The androgen-independent human prostate tumor cell line PC3 was implanted subcutaneously in the flanks of Naval Medical Research Institute (NMRI) (nu/nu) mice (n = 11). Mice-6 weeks post-xenograft implantation-were injected with 37 MBq [(11)C]CHO via the tail vein. On a separate day, the mice were injected with 37 MBq [(11)C]SMC. Dynamic imaging was performed for 60 min with the Inveon animal PET/CT scanner (Siemens Medical Solutions) on two separate days (randomizing the sequence of the tracers). The dynamic PET images were acquired in list mode. Regions of interest (5 × 5 × 5 mm) were placed in transaxial slices in tumor, muscle (thigh), liver, kidney, and blood. Image analysis was performed calculating tumor to muscle (T/M) ratios based on summed images as well as dynamic data. RESULTS For [(11)C]SMC, the mean T/M ratio was 2.24 ± 0.56 while the corresponding mean [(11)C]CHO T/M ratio was 1.35 ± 0.28. The T/M ratio for [(11)C]SMC was significant higher compared to [(11)C]CHO (p < 0.001). The time course of T/M ratio (T/Mdyn ratio) of [(11)C]SMC was higher compared to [(11)C]CHO with a statistically significant difference between the magnitudes of the T/M ratios and a significant different change of the T/M ratios over time between [(11)C]CHO and [(11)C]SMC. CONCLUSION Our results demonstrate that [(11)C]SMC is taken up by the tumor in the PC-3 prostate cancer xenograft model. [(11)C]SMC uptake was significantly higher compared to the clinically utilized [(11)C]CHO tracer with a higher contrast allowing imaging of a prostate cancer xenograft.
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Affiliation(s)
- Sarah Marie Schwarzenböck
- Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich, 81675, Munich, Germany,
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Detection of local recurrence of prostate cancer after radical prostatectomy: Is there a role for early ¹⁸F-FCH PET/CT? Ann Nucl Med 2015; 29:861-9. [PMID: 26261000 DOI: 10.1007/s12149-015-1015-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2015] [Accepted: 08/03/2015] [Indexed: 01/12/2023]
Abstract
AIM To investigate the diagnostic performance of early acquisition compared to late imaging for the detection of local recurrence of prostate cancer by means of ¹⁸F-FCH PET/CT. MATERIALS AND METHODS 99 patients with radical prostatectomy (mean PSA 3.9 ± 5.03) were subjected to early dynamic PET/CT acquisition of the pelvis and a whole body PET/CT in the same exam session. None of the patients examined was subjected to radiotherapy for local or distant recurrence. All the subjects were taken off hormonal therapy. RESULTS 58 subjects did not show local recurrence in both early and late acquisition, 22 were positive in both modalities, 10 showed a positive early and a negative late acquisition while 9 showed a negative early and a positive late acquisition (Cohen's k = 0.558). When the results of imaging modalities were considered separately, sensitivity, specificity, positive predictive value and negative predictive value resulted: 78.9, 96.7, 93.8 and 88.1 % for early acquisition and 73.7, 95.1, 90.3 and 85.3 % for late acquisition, respectively. When the results of early and late acquisition were considered together, results were 97.4, 93.4, 90.2 and 98.3 %, respectively. CONCLUSIONS The combination of early acquisition with late acquisition lead to an increase of the diagnostic accuracy of ¹⁸F-FCH PET/CT for the diagnosis of local recurrence in prostate cancer.
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Kniess T, Laube M, Brust P, Steinbach J. 2-[18F]Fluoroethyl tosylate – a versatile tool for building18F-based radiotracers for positron emission tomography. MEDCHEMCOMM 2015. [DOI: 10.1039/c5md00303b] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
The review highlights the role of 2-[18F]fluoroethyltosylate ([18F]FETs) in PET radiotracer design since it is a preferred labeling reagent according to its high reactivity to phenolic, amine, thiophenolic and carboxylic functions.
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Affiliation(s)
- Torsten Kniess
- Helmholtz-Zentrum Dresden-Rossendorf
- Institute of Radiopharmaceutical Cancer Research
- Dresden
- Germany
| | - Markus Laube
- Helmholtz-Zentrum Dresden-Rossendorf
- Institute of Radiopharmaceutical Cancer Research
- Dresden
- Germany
| | - Peter Brust
- Helmholtz-Zentrum Dresden-Rossendorf
- Institute of Radiopharmaceutical Cancer Research
- Dresden
- Germany
| | - Jörg Steinbach
- Helmholtz-Zentrum Dresden-Rossendorf
- Institute of Radiopharmaceutical Cancer Research
- Dresden
- Germany
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Wang XY, Yang F, Jin C, Fu DL. Utility of PET/CT in diagnosis, staging, assessment of resectability and metabolic response of pancreatic cancer. World J Gastroenterol 2014; 20:15580-15589. [PMID: 25400441 PMCID: PMC4229522 DOI: 10.3748/wjg.v20.i42.15580] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2013] [Revised: 01/21/2014] [Accepted: 03/12/2014] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is one of the most common gastrointestinal tumors, with its incidence staying at a high level in both the United States and China. However, the overall 5-year survival rate of pancreatic cancer is still extremely low. Surgery remains the only potential chance for long-term survival. Early diagnosis and precise staging are crucial to make proper clinical decision for surgery candidates. Despite advances in diagnostic technology such as computed tomography (CT) and endoscopic ultrasound, diagnosis, staging and monitoring of the metabolic response remain a challenge for this devastating disease. Positron emission tomography/CT (PET/CT), a relatively novel modality, combines metabolic detection with anatomic information. It has been widely used in oncology and achieves good results in breast cancer, lung cancer and lymphoma. Its utilization in pancreatic cancer has also been widely accepted. However, the value of PET/CT in pancreatic disease is still controversial. Will PET/CT change the treatment strategy for potential surgery candidates? What kind of patients benefits most from this exam? In this review, we focus on the utility of PET/CT in diagnosis, staging, and assessment of resectability of pancreatic cancer. In addition, its ability to monitor metabolic response and recurrence after treatment will be emphasis of discussion. We hope to provide answers to the questions above, which clinicians care most about.
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Takesh M. Kinetic Modeling Application to (18)F-fluoroethylcholine Positron Emission Tomography in Patients with Primary and Recurrent Prostate Cancer Using Two-tissue Compartmental Model. World J Nucl Med 2014; 12:101-10. [PMID: 25214813 PMCID: PMC4145150 DOI: 10.4103/1450-1147.136734] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Although 18F-fludeoxyglucose-positron emission tomography (PET) is the most applied diagnostic method in tumor staging, its role in prostate cancer (PCA) is limited because glucose metabolism tends to be low unless PCA has high Gleason score. Alternatively, choline PET was introduced as a valuable imaging method. Kinetic analysis of PET acquisition has increasingly gained momentum as an investigative tool because it provides a non-invasive approach to obtain kinetic and metabolic data from tissues of interest including transport and metabolism of the administered material. In this regard, we sought to apply it in 18F-fluoroethylcholine (FECH)-PET/computed tomography (CT) in patients with PCA. 64 patients, the mean age 69 (range: 47-87 years) with primary/recurrent PCA were encompassed. They underwent 18F-FECH-PET started with a dynamic acquisition using a 20-frame each 30 s over the prostate region and followed at 1 h post-injection by a static whole body imaging. The kinetic evaluation of the data was performed using the software package PMOD (PMOD Technologies Ltd., Zürich, Switzerland). Significant increase in mean values for K1, K3, FD, standardized uptake value (SUV) and global influx in tumor tissue versus normal tissue (P < 0.05). Moderate but significant correlation (r: 0.28, P = 0.023) between SUV and K1. By contrast, no correlation between SUV and K3 (r: −0.08, P = 0.79). In patients with recurrent tumors, there is no significant difference in all kinetic parameters and SUV (P > 0.1) between the different types of recurrences. The kinetic analysis of dynamic FECH-PET provides a novel method in primary PCA diagnosis and could be of potential value in the delineation of tumor focus.
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Affiliation(s)
- Mustafa Takesh
- Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg ; Department of Nuclear Medicine and Radiology, Knappschaft Hospital, 66280 Sulzbach, Germany
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Usefulness of 11C-choline positron emission tomography for genital chlamydial infection assessment in a BALB/c murine model. Mol Imaging Biol 2014; 15:450-5. [PMID: 23362001 DOI: 10.1007/s11307-013-0612-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
PURPOSE The aim of this study is to explore the feasibility of 11C-Choline PET in the assessment of the degree of inflammation in the Chlamydia muridarum genital infection model. PROCEDURES Forty female Balb/c mice received 2.5 mg of medroxyprogesterone acetate i.m. 9 and 2 days prior to the infection: 21 mice were infected by C. muridarum into the vaginal vault, 12 mice were treated with inactivated chlamydiae, and 7 mice were SPG buffer-treated as negative controls. Three healthy control mice were not treated with progesterone. Mice in each category were randomly subdivided in two groups: (1) sacrificed at 5, 10, 15, and 20 days for histological analysis and (2) undergoing 11C-Choline PET at days 5, 10, and 20 post-infection (20 MBq of 11C-Choline, uptake time of 10 min, acquisition through a small-animal PET tomograph for 15 min). RESULTS Infected animals showed a significantly higher standardized uptake value than both controls and animals inoculated with heat-inactivated chlamydiae in each PET scan (P<0.05). All organs of the infected animals had scores of inflammation ranging between 2 and 3 at day 5, decreasing to 1-2 at day 20. CONCLUSIONS This preliminary result demonstrated that 11C-Choline PET can highlight a specific proliferation mechanism of inflammatory cells induced by C. muridarum, thanks to a very high sensitivity in detecting very small amounts of tracer in inflammatory cells.
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Abstract
Prostate cancer is a heterogeneous disease, and its management is now evolving to become more personalized and to incorporate new targeted therapies. With these new changes comes a demand for molecular imaging techniques that can not only detect disease but also assess biology and treatment response. This review article summarizes current molecular imaging approaches in prostate cancer (e.g. 99mTc bone scintigraphy and 18F-fluorodeoxyglucose positron emission tomography) and highlights emerging clinical and preclinical imaging agents, with an emphasis on mechanism and clinical application. Emerging agents at various stages of clinical translation include radiolabeled analogs of lipid, amino acid, and nucleoside metabolism, as well as agents more specifically targeting prostate cancer biomarkers including androgen receptor, prostate-specific membrane antigen and others. We also highlight new techniques and targeted contrast agents for magnetic resonance imaging and spectroscopy. For all these imaging techniques, a growing and important unmet need is for well-designed prospective clinical trials to establish clear indications with clinical benefit in prostate cancer.
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Affiliation(s)
- Ana P. Kiess
- Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - Steve Y. Cho
- Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Martin G. Pomper
- Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD
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Takesh M. The Potential Benefit by Application of Kinetic Analysis of PET in the Clinical Oncology. ISRN ONCOLOGY 2012; 2012:349351. [PMID: 23326682 PMCID: PMC3541563 DOI: 10.5402/2012/349351] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/04/2012] [Accepted: 11/25/2012] [Indexed: 12/22/2022]
Abstract
PET is an appropriate method to display the functional activities in target tissue using many types of traces. The visual assessment of PET images plus the semiquantitative parameter (SUV) are the main diagnostic standards considered in identifying the malignant lesion. However, these standards lack occasionally the proper specificity and/or sensitivity. That emphasizes the importance of considering supplemental diagnostic criteria such as the kinetic parameter. The latter gives the way to image the ongoing metabolic processes within the target tissue as well as to identify the alterations occurring at the microscale level before they become observable in the conventional PET-imaging.
The importance of kinetic analysis of PET imaging has increased with newly developed PET devices that offer images of good quality and high spatial resolution.
In this paper, we highlighted the potential contribution of kinetic analysis in improving the diagnostic accuracy in intracranial tumour, lung tumour, liver tumour, colorectal tumour, bone and soft tissue tumours, and prostate cancer. Moreover, we showed that the appropriate therapy monitoring can be best achieved after considering the kinetic parameters. These promising results indicate that the kinetic analysis of PET imaging may become an essential part in preclinical and clinical molecular imaging as well.
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Affiliation(s)
- Mustafa Takesh
- Nuclear Medicine Department, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
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14
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15
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Kenny LM, Contractor KB, Hinz R, Stebbing J, Palmieri C, Jiang J, Shousha S, Al-Nahhas A, Coombes RC, Aboagye EO. Reproducibility of [11C]choline-positron emission tomography and effect of trastuzumab. Clin Cancer Res 2010; 16:4236-45. [PMID: 20682702 DOI: 10.1158/1078-0432.ccr-10-0468] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
PURPOSE This study sought to evaluate the reproducibility of [(11)C]choline-positron emission tomography and the effect of trastuzumab in breast cancer. EXPERIMENTAL DESIGN Twenty-one patients with newly diagnosed and recurrent breast cancer stage II-IV had a baseline dynamic [(11)C]choline-PET scan, 10 patients had a second [(11)C]choline-PET scan to examine reproducibility, and 6 patients had a second scan within a month after trastuzumab. Analysis of [(11)C]choline uptake was measured as the semiquantitative standardized uptake value at 30 and 60 minutes (SUV(30) and SUV(60)), and quantitatively as the net irreversible retention of the radiotracer at steady-state (Ki) and plasma to tissue exchange at 60 minutes (IRF60min). RESULTS Breast tumor lesions in all patients were visualized by [(11)C]choline PET. The difference in tumor versus normal tissue uptake was significant for SUV(30), SUV(60), Ki, and IRF60 minutes (Wilcoxon P < 0.0001). At 60 minutes postinjection, 15.1 +/- 2.16% of plasma radioactivity was due to unmetabolized [(11)C]choline radioactivity. [(11)C]Choline uptake was reproducible in breast tumor lesions (r(2) = 0.9 for SUV, 0.9 for Ki, and 0.8 for IRF60). Early responses to trastuzumab measured by [(11)C]choline-PET were significant in three lesions occurring in two patients who responded clinically. CONCLUSIONS [(11)C]Choline-PET uptake variables can be reproducibly assessed. Initial studies show that trastuzumab decreases [(11)C]choline uptake.
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Affiliation(s)
- Laura M Kenny
- Department of Cancer Medicine, Imperial College, London, UK
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Laitinen IEK, Luoto P, Någren K, Marjamäki PM, Silvola JMU, Hellberg S, Laine VJO, Ylä-Herttuala S, Knuuti J, Roivainen A. Uptake of 11C-choline in mouse atherosclerotic plaques. J Nucl Med 2010; 51:798-802. [PMID: 20395326 DOI: 10.2967/jnumed.109.071704] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
UNLABELLED The purpose of this study was to explore the feasibility of (11)C-choline in the assessment of the degree of inflammation in atherosclerotic plaques. METHODS Uptake of (11)C-choline was studied ex vivo in tissue samples and aortic sections excised from 6 atherosclerotic mice deficient for both low-density lipoprotein receptor and apolipoprotein B48 (LDLR(-/-)ApoB(100/100)) and 5 control mice. The autoradiographs were compared with the immunohistology of the arterial sites. RESULTS The uptake of (11)C-choline (percentage of the injected activity per gram of tissue) in the atherosclerotic aortas of the LDLR(-/-)ApoB(100/100) mice was significantly higher (1.9-fold, P = 0.0016) than that in the aortas of the control mice. The autoradiography analysis showed significantly higher uptake of (11)C-choline in the plaques than in healthy vessel wall (mean ratio, 2.3 +/- 0.6; P = 0.014), prominently in inflamed plaques, compared with noninflamed plaque areas. CONCLUSION We observed a high (11)C-choline uptake in the aortic plaques of atherosclerotic mice. Our data suggest that macrophages may be responsible for the uptake of (11)C-choline in the plaques.
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Pascali G, D'Antonio L, Bovone P, Gerundini P, August T. Optimization of automated large-scale production of [(18)F]fluoroethylcholine for PET prostate cancer imaging. Nucl Med Biol 2009; 36:569-74. [PMID: 19520298 DOI: 10.1016/j.nucmedbio.2009.01.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2008] [Revised: 01/02/2009] [Accepted: 01/05/2009] [Indexed: 10/21/2022]
Abstract
INTRODUCTION PET tumor imaging is gaining importance in current clinical practice. FDG-PET is the most utilized approach but suffers from inflammation influences and is not utilizable in prostate cancer detection. Recently, (11)C-choline analogues have been employed successfully in this field of imaging, leading to a growing interest in the utilization of (18)F-labeled analogues: [(18)F]fluoroethylcholine (FEC) has been demonstrated to be promising, especially in prostate cancer imaging. In this work we report an automatic radiosynthesis of this tracer with high yields, short synthesis time and ease of performance, potentially utilizable in routine production sites. METHODS We used a Modular Lab system to automatically perform the two-step/one-pot synthesis. In the first step, we labeled ethyleneglycolditosylate obtaining [(18)F]fluoroethyltosylate; in the second step, we performed the coupling of the latter intermediate with neat dimethylethanolamine. The final mixture was purified by means of solid phase extraction; in particular, the product was trapped into a cation-exchange resin and eluted with isotonic saline. RESULTS The optimized procedure resulted in a non decay corrected yield of 36% and produced a range of 30-45 GBq of product already in injectable form. The product was analyzed for quality control and resulted as pure and sterile; in addition, residual solvents were under the required threshold. CONCLUSION In this work, we present an automatic FEC radiosynthesis that has been optimized for routine production. This findings should foster the interest for a wider utilization of this radiomolecule for imaging of prostate cancer with PET, a field for which no gold-standard tracer has yet been validated.
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Molecular Imaging in Oncology. Mol Imaging 2009. [DOI: 10.1007/978-3-540-76735-0_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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Abstract
Molecular imaging of tumor metabolism has gained considerable interest, since preclinical studies have indicated a close relationship between the activation of various oncogenes and alterations of cellular metabolism. Furthermore, several clinical trials have shown that metabolic imaging can significantly impact patient management by improving tumor staging, restaging, radiation treatment planning, and monitoring of tumor response to therapy. In this review, we summarize recent data on the molecular mechanisms underlying the increased metabolic activity of cancer cells and discuss imaging techniques for studies of tumor glucose, lipid, and amino acid metabolism.
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Affiliation(s)
- Christian Plathow
- Department of Nuclear Medicine, University of Freiburg, Freiburg, Germany
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Langer HF, Haubner R, Pichler BJ, Gawaz M. Radionuclide imaging: a molecular key to the atherosclerotic plaque. J Am Coll Cardiol 2008; 52:1-12. [PMID: 18582628 PMCID: PMC2683742 DOI: 10.1016/j.jacc.2008.03.036] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2008] [Revised: 03/20/2008] [Accepted: 03/24/2008] [Indexed: 01/09/2023]
Abstract
Despite primary and secondary prevention, serious cardiovascular events such as unstable angina or myocardial infarction still account for one-third of all deaths worldwide. Therefore, identifying individual patients with vulnerable plaques at high risk for plaque rupture is a central challenge in cardiovascular medicine. Several noninvasive techniques, such as magnetic resonance imaging, multislice computed tomography, and electron beam tomography are currently being tested for their ability to identify such patients by morphological criteria. In contrast, molecular imaging techniques use radiolabeled molecules to detect functional aspects in atherosclerotic plaques by visualizing their biological activity. Based upon the knowledge about the pathophysiology of atherosclerosis, various studies in vitro and in vivo and the first clinical trials have used different tracers for plaque imaging studies, including radioactive-labeled lipoproteins, components of the coagulation system, cytokines, mediators of the metalloproteinase system, cell adhesion receptors, and even whole cells. This review gives an update on the relevant noninvasive plaque imaging approaches using nuclear imaging techniques to detect atherosclerotic vascular lesions.
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Affiliation(s)
- Harald F Langer
- Medizinische Klinik III, Eberhard Karls Universität Tübingen, Tübingen, Germany.
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Guha C, Alfieri A, Blaufox MD, Kalnicki S. Tumor biology-guided radiotherapy treatment planning: gross tumor volume versus functional tumor volume. Semin Nucl Med 2008; 38:105-13. [PMID: 18243845 DOI: 10.1053/j.semnuclmed.2007.12.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
This issue of Seminars in Nuclear Medicine deals with a watershed event in cancer treatment -- the combined use of functional and anatomical information to guide therapeutic interventions. The use of positron emission tomography/computed tomography (PET/CT) in radiation treatment planning and tumor response evaluation brings a paradigm change in the development of image-guided therapies into routine clinical practice. The implications, as seen in the following articles, are not only promising but also groundbreaking. And, as in every new scientific breakthrough, each step forward generates a myriad of additional important clinical and research questions. Functional imaging takes advantage of the subtle differences between normal and malignant tissues at the cellular level to reveal in vivo unique functional characteristics of neoplasms. The ultimate goal of the partnership between nuclear medicine physicians and radiation oncologists is to use this information with absolute clarity in target definition for radiation treatment planning and therapy, as well as response evaluation. Functional imaging can provide metabolic information and behavioral correlation along with the anatomical imaging for correlative target delineation. Additionally, as a purely diagnostic instrument, PET/CT provides a tool for oncologists to make critical decisions regarding radiation treatment planning modifications secondary to changes in tumor staging (up or down), treatment field modifications, localized control, sites of residual and/or metastatic disease and post therapy response evaluation. The articles in this issue of the seminars provide insights into the current state-of-the-art of functional imaging techniques, mostly centered on the use of (18)F-fluorodeoxyglucose PET/CT in image guided oncologic therapies. Because it is a novel science, the future of image-guided functional treatment planning is bright with technologic and biologic innovations, translational research and new clinical applications.
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Affiliation(s)
- Chandan Guha
- Department Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10467, USA.
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22
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Vallabhajosula S. (18)F-labeled positron emission tomographic radiopharmaceuticals in oncology: an overview of radiochemistry and mechanisms of tumor localization. Semin Nucl Med 2008; 37:400-19. [PMID: 17920348 DOI: 10.1053/j.semnuclmed.2007.08.004] [Citation(s) in RCA: 147] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Molecular imaging is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in a living system. At present, positron emission tomography/computed tomography (PET/CT) is one the most rapidly growing areas of medical imaging, with many applications in the clinical management of patients with cancer. Although [(18)F]fluorodeoxyglucose (FDG)-PET/CT imaging provides high specificity and sensitivity in several kinds of cancer and has many applications, it is important to recognize that FDG is not a "specific" radiotracer for imaging malignant disease. Highly "tumor-specific" and "tumor cell signal-specific" PET radiopharmaceuticals are essential to meet the growing demand of radioisotope-based molecular imaging technology. In the last 15 years, many alternative PET tracers have been proposed and evaluated in preclinical and clinical studies to characterize the tumor biology more appropriately. The potential clinical utility of several (18)F-labeled radiotracers (eg, fluoride, FDOPA, FLT, FMISO, FES, and FCH) is being reviewed by several investigators in this issue. An overview of design and development of (18)F-labeled PET radiopharmaceuticals, radiochemistry, and mechanism(s) of tumor cell uptake and localization of radiotracers are presented here. The approval of clinical indications for FDG-PET in the year 2000 by the Food and Drug Administration, based on a review of literature, was a major breakthrough to the rapid incorporation of PET into nuclear medicine practice, particularly in oncology. Approval of a radiopharmaceutical typically involves submission of a "New Drug Application" by a manufacturer or a company clearly documenting 2 major aspects of the drug: (1) manufacturing of PET drug using current good manufacturing practices and (2) the safety and effectiveness of a drug with specific indications. The potential routine clinical utility of (18)F-labeled PET radiopharmaceuticals depends also on regulatory compliance in addition to documentation of potential safety and efficacy by various investigators.
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Affiliation(s)
- Shankar Vallabhajosula
- Division of Nuclear Medicine, Department of Radiology,New York Presbyterian Hospital, Cornell University, New York, NY 10021, USA.
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23
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Feasibility of 18F-fluoromethylcholine PET/CT for imaging of vessel wall alterations in humans—first results. Eur J Nucl Med Mol Imaging 2008; 35:815-20. [DOI: 10.1007/s00259-007-0685-x] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2007] [Accepted: 12/03/2007] [Indexed: 10/22/2022]
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Schulte RW, Li T. Innovative strategies for image-guided proton treatment of prostate cancer. Technol Cancer Res Treat 2006; 5:91-100. [PMID: 16551129 DOI: 10.1177/153303460600500203] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Proton beam therapy has a proven track record of treating non-metastatic prostate cancer with excellent disease-free survival results when using homogeneous doses between 75 and 82 CGE (Cobalt Gray Equivalent) to the prostate target volume. In clinically organ-confined prostate cancer, it may be possible, in principle, to further improve outcomes by reducing the margins of the high-dose planning target volume to the gross tumor volume and by covering the clinical target volume with a dose sufficient to control microscopic extensions of the tumor. This would allow further dose escalation without increasing the risk of acute and late effects. In this paper, we undertake a careful review of existing histopathological data that support this view and discuss technical possibilities to this approach utilizing the highly conformal characteristics of proton beams and combining them with modern 4D imaging and treatment techniques.
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Affiliation(s)
- Reinhard W Schulte
- Department of Radiation Medicine, Loma Linda University Medical Center, Loma Linda, CA, USA.
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25
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Spaeth N, Wyss MT, Pahnke J, Biollaz G, Lutz A, Goepfert K, Westera G, Treyer V, Weber B, Buck A. Uptake of 18F-fluorocholine, 18F-fluoro-ethyl-L-tyrosine and 18F-fluoro-2-deoxyglucose in F98 gliomas in the rat. Eur J Nucl Med Mol Imaging 2006; 33:673-82. [PMID: 16538503 DOI: 10.1007/s00259-005-0045-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2005] [Accepted: 11/16/2005] [Indexed: 10/24/2022]
Abstract
INTRODUCTION The positron emission tomography (PET) tracers (18)F-fluoro-ethyl-L: -tyrosine (FET), (18)F-fluorocholine (N,N-dimethyl-N-[(18)F]fluoromethyl-2-hydroxyethylammonium (FCH]) and (18)F-fluoro-2-deoxyglucose (FDG) are used in the diagnosis of brain tumours. The aim of this study was threefold: (a) to assess the uptake of the different tracers in the F98 rat glioma, (b) to evaluate the impact of blood-brain barrier (BBB) disruption and microvessel density (MVD) on tracer uptake and (c) to compare the uptake in the tumours to that in the radiation injuries (induced by proton irradiation of healthy rats) of our previous study. METHODS F98 gliomas were induced in 26 rats. The uptake of FET, FCH and FDG was measured using autoradiography and correlated with histology, disruption of the BBB and MVD. RESULTS The mean FET, FCH and FDG standardised uptake values (SUVs) in the tumour and the contralateral normal cortex (in parentheses) were 4.19+/-0.86 (1.32+/-0.26), 2.98+/-0.58 (0.51+/-0.11) and 11.02+/-3.84 (4.76+/-1.77) respectively. MVD was significantly correlated only with FCH uptake. There was a trend towards a negative correlation between the degree of BBB disruption and FCH uptake and a trend towards a positive correlation with FET uptake. The ratio of the uptake in tumours to that in the radiation injuries was 1.97 (FCH), 2.71 (FET) and 2.37 (FDG). CONCLUSION MVD displayed a significant effect only on FCH uptake. The degree of BBB disruption seems to affect the accumulation of FET and FCH, but not FDG. Mean tumour uptake for all tracers was significantly higher than the accumulation in radiation injuries.
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Affiliation(s)
- Nicolas Spaeth
- PET Center, Division of Nuclear Medicine, University Hospital, Rämistrasse 100, 8091, Zürich, Switzerland
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Matter CM, Wyss MT, Meier P, Späth N, von Lukowicz T, Lohmann C, Weber B, Ramirez de Molina A, Lacal JC, Ametamey SM, von Schulthess GK, Lüscher TF, Kaufmann PA, Buck A. 18F-choline images murine atherosclerotic plaques ex vivo. Arterioscler Thromb Vasc Biol 2005; 26:584-9. [PMID: 16357314 DOI: 10.1161/01.atv.0000200106.34016.18] [Citation(s) in RCA: 88] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
OBJECTIVE Current imaging modalities of atherosclerosis mainly visualize plaque morphology. Valuable insight into plaque biology was achieved by visualizing enhanced metabolism in plaque-derived macrophages using 18F-fluorodeoxyglucose (18F-FDG). Similarly, enhanced uptake of 18F-fluorocholine (18F-FCH) was associated with macrophages surrounding an abscess. As macrophages are important determinants of plaque vulnerability, we tested 18F-FCH for plaque imaging. METHODS AND RESULTS We injected 18F-FCH (n=5) or 18F-FDG (n=5) intravenously into atherosclerotic apolipoprotein E-deficient mice. En face measurements of aortae isolated 20 minutes after 18F-FCH injections demonstrated an excellent correlation between fat stainings and autoradiographies (r=0.842, P<0.0001), achieving a sensitivity of 84% to detect plaques by 18F-FCH. In contrast, radiotracer uptake 20 minutes after 18F-FDG injections correlated less with en face fat stainings (r=0.261, P<0.05), reaching a sensitivity of 64%. Histological analyses of cross-sections 20 minutes after coinjections of 18F-FCH and 14C-FDG (n=3) showed that 18F-FCH uptake correlated better with fat staining (r=0.740, P<0.0001) and macrophage-positive areas (r=0.740, P<0.0001) than 14C-FDG (fat: r=0.236, P=0.29 and CD68 staining: r=0.352, P=0.11), respectively. CONCLUSIONS 18F-FCH identifies murine plaques better than 18F-FDG using ex vivo imaging. Enhanced 18F-FCH uptake into macrophages may render this tracer a promising candidate for imaging plaques in patients.
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Affiliation(s)
- Christian M Matter
- Cardiovascular Research, Institute of Physiology, University of Zurich, Cardiovascular Center, Switzerland.
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Iorio E, Mezzanzanica D, Alberti P, Spadaro F, Ramoni C, D'Ascenzo S, Millimaggi D, Pavan A, Dolo V, Canevari S, Podo F. Alterations of Choline Phospholipid Metabolism in Ovarian Tumor Progression. Cancer Res 2005; 65:9369-76. [PMID: 16230400 DOI: 10.1158/0008-5472.can-05-1146] [Citation(s) in RCA: 224] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Recent characterization of abnormal phosphatidylcholine metabolism in tumor cells by nuclear magnetic resonance (NMR) has identified novel fingerprints of tumor progression that are potentially useful as clinical diagnostic indicators. In the present study, we analyzed the concentrations of phosphatidylcholine metabolites, activities of phosphocholine-producing enzymes, and uptake of [methyl-14C]choline in human epithelial ovarian carcinoma cell lines (EOC) compared with normal or immortalized ovary epithelial cells (EONT). Quantification of phosphatidylcholine metabolites contributing to the 1H NMR total choline resonance (3.20-3.24 ppm) revealed intracellular [phosphocholine] and [total choline] of 2.3 +/- 0.9 and 5.2 +/- 2.4 nmol/10(6) cells, respectively, with a glycerophosphocholine/phosphocholine ratio of 0.95 +/- 0.93 in EONT cells; average [phosphocholine] was 3- to 8-fold higher in EOC cells (P < 0.0001), becoming the predominant phosphatidylcholine metabolite, whereas average glycerophosphocholine/phosphocholine values decreased significantly to < or =0.2. Two-dimensional (phosphocholine/total choline, [total choline]) and (glycerophosphocholine/total choline, [total choline]) maps allowed separate clustering of EOC from EONT cells (P < 0.0001, 95% confidence limits). Rates of choline kinase activity in EOC cells were 12- to 24-fold higher (P < 0.03) than those in EONT cells (basal rate, 0.5 +/- 0.1 nmol/10(6) cells/h), accounting for a consistently elevated (5- to 15-fold) [methyl-14C]choline uptake after 1-hour incubation (P < 0.0001). The overall activity of phosphatidylcholine-specific phospholipase C and phospholipase D was also higher ( approximately 5-fold) in EOC cells, suggesting that both biosynthetic and catabolic pathways of the phosphatidylcholine cycle likely contribute to phosphocholine accumulation. Evidence of abnormal phosphatidylcholine metabolism might have implications in EOC biology and might provide an avenue to the development of noninvasive clinical tools for EOC diagnosis and treatment follow-up.
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Affiliation(s)
- Egidio Iorio
- Section of Molecular and Cellular Imaging, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
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