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Gulhane AV, Chen DL. Overview of positron emission tomography in functional imaging of the lungs for diffuse lung diseases. Br J Radiol 2022; 95:20210824. [PMID: 34752146 PMCID: PMC9153708 DOI: 10.1259/bjr.20210824] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Positron emission tomography (PET) is a quantitative molecular imaging modality increasingly used to study pulmonary disease processes and drug effects on those processes. The wide range of drugs and other entities that can be radiolabeled to study molecularly targeted processes is a major strength of PET, thus providing a noninvasive approach for obtaining molecular phenotyping information. The use of PET to monitor disease progression and treatment outcomes in DLD has been limited in clinical practice, with most of such applications occurring in the context of research investigations under clinical trials. Given the high costs and failure rates for lung drug development efforts, molecular imaging lung biomarkers are needed not only to aid these efforts but also to improve clinical characterization of these diseases beyond canonical anatomic classifications based on computed tomography. The purpose of this review article is to provide an overview of PET applications in characterizing lung disease, focusing on novel tracers that are in clinical development for DLD molecular phenotyping, and briefly address considerations for accurately quantifying lung PET signals.
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Affiliation(s)
- Avanti V Gulhane
- Department of Radiology, University of Washington School of Medicine, Seattle, United States
| | - Delphine L Chen
- Department of Radiology, University of Washington School of Medicine, Seattle, United States
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Porter JC, Win T, Erlandsson K, Thielemans K, Groves AM. Reply: Measurement of hypoxia in the lung in idiopathic pulmonary fibrosis: a matter of control. Eur Respir J 2022; 59:13993003.03124-2021. [PMID: 35086831 PMCID: PMC8907934 DOI: 10.1183/13993003.03124-2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 01/10/2022] [Indexed: 01/26/2023]
Abstract
We thank P-S. Bellaye and co-workers for their considered and insightful response. Given their finding of [18F]fluoromisonidazole ([18F]F-MISO) uptake in the bleomycin mouse model of fibrosis [1], we too were surprised not to demonstrate a similar signal in patients with idiopathic pulmonary fibrosis (IPF). However, as acknowledged, there are other examples of positron emission tomography (PET) tracers, such as cis-4-[18F]-fluoro-l-proline, yielding PET signals in animal lung fibrosis models that have not been replicated in humans with fibrotic lung disease [2, 3]. In vivo PET imaging in IPF patients shows no significant evidence of lung tissue hypoxiahttps://bit.ly/3fywY7K
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Affiliation(s)
- Joanna C. Porter
- Centre for Inflammation and Tissue Repair, UCL and the UCLH Interstitial Lung Disease Service, London, UK,Joanna C. Porter ()
| | - Thida Win
- Respiratory Medicine, Lister Hospital, Stevenage, UK
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3
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Xiong Y, Nie D, Liu S, Ma H, Su S, Sun A, Zhao J, Zhang Z, Xiang X, Tang G. Apoptotic PET Imaging of Rat Pulmonary Fibrosis With [ 18F]ML-8. Mol Imaging 2019; 17:1536012118795728. [PMID: 30348035 PMCID: PMC6201178 DOI: 10.1177/1536012118795728] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Objective: To investigate the value of 2-(3-[18F]fluoropropyl)-2-methyl-malonic acid
([18F]ML-8) positron emission tomography (PET) imaging of rat pulmonary
fibrosis. Methods: Male Sprague-Dawley rats were divided into 2 groups, including pulmonary fibrosis model
group and control group. The rat model was established by an intratracheal instillation
of bleomycin (BLM). Control rats were treated with saline. Positron emission
tomography/computed tomography (CT) with [18F]ML-8 or
18F-fluorodeoxyglucose ([18F]FDG) was performed on 2 groups. After
PET/CT imaging, lung tissues were collected for histologic examination. Data were
analyzed and comparisons between 2 groups were performed using Student
t test. Results: Bleomycin-treated rats showed a higher lung uptake of [18F]ML-8 than control
rats (P < .05). In BLM-treated rats, the lung to muscle relative
uptake ratio of [18F]ML-8 was also higher than that of [18F]FDG
(P < .05). Pathological examination showed overproliferation of
fibroblasts and deposition of collagen in lungs from BLM-treated rats. Compared to
control rats, BLM-treated rats had higher lung hydroxyproline content
(P < .05). Immunofluorescence staining indicated more apoptotic
cells in BLM-treated rats than those in control rats. Moreover, the apoptosis rate of
lung tissues obtained from BLM-treated rats was higher than that from control rats
(P < .05). Conclusions: 2-(3-[18F]fluoropropyl)-2-methyl-malonic acid PET/CT could be used for
noninvasive diagnosis of pulmonary fibrosis in a rat model.
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Affiliation(s)
- Ying Xiong
- 1 Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals and Department of Medical Imaging, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Dahong Nie
- 1 Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals and Department of Medical Imaging, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shaoyu Liu
- 1 Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals and Department of Medical Imaging, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Hui Ma
- 1 Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals and Department of Medical Imaging, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shu Su
- 1 Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals and Department of Medical Imaging, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Aixia Sun
- 1 Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals and Department of Medical Imaging, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jing Zhao
- 1 Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals and Department of Medical Imaging, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhanwen Zhang
- 1 Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals and Department of Medical Imaging, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xianhong Xiang
- 1 Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals and Department of Medical Imaging, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ganghua Tang
- 1 Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals and Department of Medical Imaging, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Xiong Y, Nie D, Liu S, Ma H, Su S, Sun A, Zhao J, Zhang Z, Xiang X, Tang G. Apoptotic PET Imaging of Rat Pulmonary Fibrosis with Small-Molecule Radiotracer. Mol Imaging Biol 2018; 21:491-499. [PMID: 30167994 DOI: 10.1007/s11307-018-1242-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE The purpose of this study was to assess the potential utility of small-molecule apoptotic radiotracer, 2-(5-[18F]fluoropentyl)-2-methyl malonic acid ([18F]ML-10), for positron emission tomography (PET)/computed tomography (CT) monitoring the progression of pulmonary fibrosis in a rat model. PROCEDURES Male Sprague-Dawley rats were used to establish a rat model of pulmonary fibrosis by means of bleomycin (BLM) administration; control rats received saline (n = 12 per group). PET/CT with [18F]ML-10 and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) was performed in two groups at different stages of pulmonary fibrosis. The fibrotic response and the cell apoptosis were assessed with histologic examination. Differences in the apoptosis rate, fibrotic activity, and the lung uptake of [18F]ML-10 and [18F]FDG between two groups were determined with Student t test. RESULTS Compared with control group, BLM group showed a higher lung uptake of [18F]ML-10 at all imaging time points (all P < 0.001). During the fibrotic phase of this disease model (days 21 and 28), the lung uptake of [18F]ML-10 was higher than that of [18F]FDG in the BLM group (all P < 0.001). Moreover, accumulation of [18F]ML-10 in the lung tissues increased in proportion to the apoptosis rate (R2 = 0.9863, P < 0.0001) and fibrotic activity (R2 = 0.9631, P < 0.0001) of rat pulmonary fibrosis. Conversely, no correlation between [18F]FDG uptake and fibrotic activity was found. CONCLUSIONS [18F]ML-10 PET/CT enabled monitoring the progression of rat pulmonary fibrosis, whereas [18F]FDG PET/CT could not. Implications for noninvasive diagnosis of pulmonary fibrosis, assessment of fibrotic activity, and evaluation of antifibrotic therapy are expected.
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Affiliation(s)
- Ying Xiong
- Department of Medical Imaging and Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080, China
| | - Dahong Nie
- Department of Medical Imaging and Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080, China
| | - Shaoyu Liu
- Department of Medical Imaging and Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080, China
| | - Hui Ma
- Department of Medical Imaging and Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080, China
| | - Shu Su
- Department of Medical Imaging and Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080, China
| | - Aixia Sun
- Department of Medical Imaging and Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080, China
| | - Jing Zhao
- Department of Medical Imaging and Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080, China
| | - Zhanwen Zhang
- Department of Medical Imaging and Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080, China
| | - Xianhong Xiang
- Department of Medical Imaging and Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080, China.
| | - Ganghua Tang
- Department of Medical Imaging and Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080, China.
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Wallbaum P, Rohde S, Ehlers L, Lange F, Hohn A, Bergner C, Schwarzenböck SM, Krause BJ, Jaster R. Antifibrogenic effects of vitamin D derivatives on mouse pancreatic stellate cells. World J Gastroenterol 2018; 24:170-178. [PMID: 29375203 PMCID: PMC5768936 DOI: 10.3748/wjg.v24.i2.170] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Revised: 11/15/2017] [Accepted: 11/27/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To study the molecular effects of three different D-vitamins, vitamin D2, vitamin D3 and calcipotriol, in pancreatic stellate cells (PSCs).
METHODS Quiescent PSCs were isolated from mouse pancreas and activated in vitro by seeding on plastic surfaces. The cells were exposed to D-vitamins as primary cultures (early-activated PSCs) and upon re-culturing (fully-activated cells). Exhibition of vitamin A-containing lipid droplets was visualized by oil-red staining. Expression of α-smooth muscle actin (α-SMA), a marker of PSC activation, was monitored by immunofluorescence and immunoblot analysis. The rate of DNA synthesis was quantified by 5-bromo-2’-deoxyuridine (BrdU) incorporation assays. Real-time PCR was employed to monitor gene expression, and protein levels of interleukin-6 (IL-6) were measured by ELISA. Uptake of proline was determined using 18F-proline.
RESULTS Sustained culture of originally quiescent PSCs induced cell proliferation, loss of lipid droplets and exhibition of stress fibers, indicating cell activation. When added to PSCs in primary culture, all three D-vitamins diminished expression of α-SMA (to 32%-39% of the level of control cells; P < 0.05) and increased the storage of lipids (scores from 1.97-2.15 on a scale from 0-3; controls: 1.49; P < 0.05). No such effects were observed when Dvitamins were added to fully-activated cells, while incorporation of BrdU remained unaffected under both experimental conditions. Treatment of re-cultured PSCs with Dvitamins was associated with lower expression of IL-6 (-42% to -49%; P < 0.05; also confirmed at the protein level) and increased expression of the vitamin D receptor gene (209%-321% vs controls; P < 0.05). There was no effect of Dvitamins on the expression of transforming growth factor-β1 and collagen type 1 (chain α1). The lowest uptake of proline, a main component of collagen, was observed in calcipotriol-treated PSCs.
CONCLUSION The three D-vitamins inhibit, with similar efficiencies, activation of PSCs in vitro, but cannot reverse the phenotype once the cells are fully activated.
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Affiliation(s)
- Peter Wallbaum
- Department of Medicine II, Division of Gastroenterology, Rostock University Medical Center, Rostock 18057, Germany
| | - Sarah Rohde
- Department of Medicine II, Division of Gastroenterology, Rostock University Medical Center, Rostock 18057, Germany
| | - Luise Ehlers
- Department of Medicine II, Division of Gastroenterology, Rostock University Medical Center, Rostock 18057, Germany
| | - Falko Lange
- Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, Rostock 18057, Germany
| | - Alexander Hohn
- Department of Nuclear Medicine, Rostock University Medical Center, Rostock 18057, Germany
| | - Carina Bergner
- Department of Nuclear Medicine, Rostock University Medical Center, Rostock 18057, Germany
| | | | - Bernd Joachim Krause
- Department of Nuclear Medicine, Rostock University Medical Center, Rostock 18057, Germany
| | - Robert Jaster
- Department of Medicine II, Division of Gastroenterology, Rostock University Medical Center, Rostock 18057, Germany
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Bondue B, Sherer F, Van Simaeys G, Doumont G, Egrise D, Yakoub Y, Huaux F, Parmentier M, Rorive S, Sauvage S, Lacroix S, Vosters O, De Vuyst P, Goldman S. PET/CT with 18F-FDG- and 18F-FBEM-labeled leukocytes for metabolic activity and leukocyte recruitment monitoring in a mouse model of pulmonary fibrosis. J Nucl Med 2015; 56:127-32. [PMID: 25537989 DOI: 10.2967/jnumed.114.147421] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
UNLABELLED Idiopathic pulmonary fibrosis is characterized by a progressive and irreversible respiratory failure. Validated noninvasive methods able to assess disease activity are essential for prognostic purposes as well as for the evaluation of emerging antifibrotic treatments. METHODS C57BL/6 mice were used in a murine model of pulmonary fibrosis induced by an intratracheal instillation of bleomycin (control mice were instilled with a saline solution). At different times after instillation, PET/CT with (18)F-FDG- or (18)F-4-fluorobenzamido-N-ethylamino-maleimide ((18)F-FBEM)-labeled leukocytes was performed to assess metabolic activity and leukocyte recruitment, respectively. RESULTS In bleomycin-treated mice, a higher metabolic activity was measured on (18)F-FDG PET/CT scans from day 7 to day 24 after instillation, with a peak of activity measured at day 14. Of note, lung mean standardized uptake values correlated with bleomycin doses, histologic score of fibrosis, lung hydroxyproline content, and weight loss. Moreover, during the inflammatory phase of the model (day 7), but not the fibrotic phase (day 23), bleomycin-treated mice presented with an enhanced leukocyte recruitment as assessed by (18)F-FBEM-labeled leukocyte PET/CT. Autoradiographic analysis of lung sections and CD45 immunostaining confirm the higher and early recruitment of leukocytes in bleomycin-treated mice, compared with control mice. CONCLUSION (18)F-FDG- and (18)F-FBEM-labeled leukocyte PET/CT enable monitoring of metabolic activity and leukocyte recruitment in a mouse model of pulmonary fibrosis. Implications for preclinical evaluation of antifibrotic therapy are expected.
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Affiliation(s)
- Benjamin Bondue
- Service de Pneumologie, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (I.R.I.B.H.M.), Université Libre de Bruxelles, Brussels, Belgium
| | - Félicie Sherer
- Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles, Gosselies, Belgium Service de Médecine Nucléaire, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; and
| | - Gaetan Van Simaeys
- Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles, Gosselies, Belgium Service de Médecine Nucléaire, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; and
| | - Gilles Doumont
- Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles, Gosselies, Belgium Service de Médecine Nucléaire, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; and
| | - Dominique Egrise
- Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles, Gosselies, Belgium Service de Médecine Nucléaire, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; and
| | - Yousof Yakoub
- Centre for Toxicology and Applied Pharmacology, Université Catholique de Louvain, Louvain-la-Neuve, Belgium
| | - François Huaux
- Centre for Toxicology and Applied Pharmacology, Université Catholique de Louvain, Louvain-la-Neuve, Belgium
| | - Marc Parmentier
- Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (I.R.I.B.H.M.), Université Libre de Bruxelles, Brussels, Belgium
| | - Sandrine Rorive
- Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles, Gosselies, Belgium
| | - Sébastien Sauvage
- Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles, Gosselies, Belgium
| | - Simon Lacroix
- Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles, Gosselies, Belgium Service de Médecine Nucléaire, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; and
| | - Olivier Vosters
- Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (I.R.I.B.H.M.), Université Libre de Bruxelles, Brussels, Belgium
| | - Paul De Vuyst
- Service de Pneumologie, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Serge Goldman
- Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles, Gosselies, Belgium Service de Médecine Nucléaire, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; and
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Behnam Azad B, Ashique R, Labiris NR, Chirakal R. Temperature effects on the stereospecificity of nucleophilic fluorination: formation of trans-[18F]4-fluoro-l-proline during the synthesis of cis-[18F]4-fluoro-l-proline. J Labelled Comp Radiopharm 2011. [DOI: 10.1002/jlcr.1947] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
| | - Rezwan Ashique
- Department of Nuclear Medicine; Hamilton Health Sciences; MUMC Site; Hamilton; ON; L8N 3Z5; Canada
| | - N. Renée Labiris
- Department of Medicine; McMaster University; Hamilton; ON; L8S 4K1; Canada
| | - Raman Chirakal
- Department of Nuclear Medicine; Hamilton Health Sciences; MUMC Site; Hamilton; ON; L8N 3Z5; Canada
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Abstract
The role of fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in the diagnosis, staging, and monitoring of neoplastic conditions is well established. The clinical utility of PET/CT has now expanded to the diagnosis of autoimmune, inflammatory, infectious, as well as non-neoplastic conditions, such as the vasculitides, atherosclerosis, and granulomatous conditions, including sarcoidosis and inflammatory bowel disease, in addition to a variety of neurologic disorders. The availability of new PET radiotracers is expected to expand PET/CT applications to a variety of other clinical domains. New radioligands for studying inflammation and neurodegenerative processes are under development. Here, we discuss the evolving potential role of PET imaging for the evaluation and monitoring of miscellaneous conditions, including osteoarthritis, interstitial lung disease, vascular thromboses, and osteoporosis.
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Affiliation(s)
- Mandana Hashefi
- Division of Rheumatology, George Washington University, Washington, District of Columbia, USA.
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Lambrou T, Groves AM, Erlandsson K, Screaton N, Endozo R, Win T, Porter JC, Hutton BF. The importance of correction for tissue fraction effects in lung PET: preliminary findings. Eur J Nucl Med Mol Imaging 2011; 38:2238-46. [PMID: 21874321 DOI: 10.1007/s00259-011-1906-x] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2011] [Accepted: 08/04/2011] [Indexed: 12/18/2022]
Abstract
PURPOSE It has recently been recognized that PET/CT may play a role in diffuse parenchymal lung disease. However, interpretation can be confounded due to the variability in lung density both within and between individuals. To address this issue a novel correction method is proposed. METHODS A CT scan acquired during shallow breathing is registered to a PET study and smoothed so as to match the PET resolution. This is used to derive voxel-based tissue fraction correction factors for the individual. The method was evaluated in a lung phantom study in which the lung was simulated by a Styrofoam/water mixture. The method was further evaluated using (18)F-FDG in 12 subjects free from pulmonary disease where ranges before and after correction were considered. RESULTS Correction resulted in similar activity concentrations for the lung and background regions, consistent with the experimental phantom set-up. Correction resulted in reduced inter- and intrasubject variability in the estimated SUV. The possible application of the method was further demonstrated in five subjects with interstitial lung changes where increased SUV was demonstrated. Single study pre- and post-treatment studies were also analysed to further illustrate the utility of the method. CONCLUSION The proposed tissue fraction correction method is a promising technique to account for variability of density in interpreting lung PET studies.
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Affiliation(s)
- Tryphon Lambrou
- Institute of Nuclear Medicine, University College London, 235 Euston Road (T5), London NW1 2BU, UK
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10
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Scheuch G, Bennett W, Borgström L, Clark A, Dalby R, Dolovich M, Fleming J, Gehr P, Gonda I, O'Callaghan C, Taylor G, Newman S. Deposition, imaging, and clearance: what remains to be done? J Aerosol Med Pulm Drug Deliv 2011; 23 Suppl 2:S39-57. [PMID: 21133799 DOI: 10.1089/jamp.2010.0839] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Deposition and clearance studies are used during product development and in fundamental research. These studies mostly involve radionuclide imaging, but pharmacokinetic methods are also used to assess the amount of drug absorbed through the lungs, which is closely related to lung deposition. Radionuclide imaging may be two-dimensional (gamma scintigraphy or planar imaging), or three-dimensional (single photon emission computed tomography and positron emission tomography). In October 2009, a group of scientists met at the "Thousand Years of Pharmaceutical Aerosols" conference in Reykjavik, Iceland, to discuss future research in key areas of pulmonary drug delivery. This article reports the session on "Deposition, imaging and clearance." The objective was partly to review our current understanding, but more importantly to assess "what remains to be done?" A need to standardize methodology and provide a regulatory framework by which data from radionuclide imaging methods could be compared between centers and used in the drug approval process was recognized. There is also a requirement for novel radiolabeling methods that are more representative of production processes for dry powder inhalers and pressurized metered dose inhalers. A need was identified for studies to aid our understanding of the relationship between clinical effects and regional deposition patterns of inhaled drugs. A robust methodology to assess clearance from small conducting airways should be developed, as a potential biomarker for therapies in cystic fibrosis and other diseases. The mechanisms by which inhaled nanoparticles are removed from the lungs, and the factors on which their removal depends, require further investigation. Last, and by no means least, we need a better understanding of patient-related factors, including how to reduce the variability in pulmonary drug delivery, in order to improve the precision of deposition and clearance measurements.
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11
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Skovgaard D, Kjaer A, Heinemeier KM, Brandt-Larsen M, Madsen J, Kjaer M. Use of cis-[18F]fluoro-proline for assessment of exercise-related collagen synthesis in musculoskeletal connective tissue. PLoS One 2011; 6:e16678. [PMID: 21347251 PMCID: PMC3037959 DOI: 10.1371/journal.pone.0016678] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2010] [Accepted: 12/23/2010] [Indexed: 01/28/2023] Open
Abstract
Protein turnover in collagen rich tissue is influenced by exercise, but can only with difficulty be studied in vivo due to use of invasive procedure. The present study was done to investigate the possibility of applying the PET-tracer, cis-[18F]fluoro-proline (cis-Fpro), for non-invasive assessment of collagen synthesis in rat musculoskeletal tissues at rest and following short-term (3 days) treadmill running. Musculoskeletal collagen synthesis was studied in rats at rest and 24 h post-exercise. At each session, rats were PET scanned at two time points following injection of cis-FPro: (60 and 240 min p.i). SUV were calculated for Achilles tendon, calf muscle and tibial bone. The PET-derived results were compared to mRNA expression of collagen type I and III. Tibial bone had the highest SUV that increased significantly (p<0.001) from the early (60 min) to the late (240 min) PET scan, while SUV in tendon and muscle decreased (p<0.001). Exercise had no influence on SUV, which was contradicted by an increased gene expression of collagen type I and III in muscle and tendon. The clearly, visible uptake of cis-Fpro in the collagen-rich musculoskeletal tissues is promising for multi-tissue studies in vivo. The tissue-specific differences with the highest basal uptake in bone are in accordance with earlier studies relying on tissue incorporation of isotopic-labelled proline. A possible explanation of the failure to demonstrate enhanced collagen synthesis following exercise, despite augmented collagen type I and III transcription, is that SUV calculations are not sensitive enough to detect minor changes in collagen synthesis. Further studies including kinetic compartment modeling must be performed to establish whether cis-Fpro can be used for non-invasive in-vivo assessment of exercise-induced changes in musculoskeletal collagen synthesis.
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Affiliation(s)
- Dorthe Skovgaard
- Institute of Sports Medicine Copenhagen, Bispebjerg Hospital and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
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12
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Ambrosini V, Zompatori M, De Luca F, Antonia D, Allegri V, Nanni C, Malvi D, Tonveronachi E, Fasano L, Fabbri M, Fanti S. 68Ga-DOTANOC PET/CT allows somatostatin receptor imaging in idiopathic pulmonary fibrosis: preliminary results. J Nucl Med 2010; 51:1950-5. [PMID: 21078794 DOI: 10.2967/jnumed.110.079962] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
UNLABELLED Interstitial lung diseases include different clinical entities with variable prognoses. Idiopathic pulmonary fibrosis (IPF), the most common, presents the most severe outcome (death within 3-5 y), whereas nonspecific interstitial pneumonia (NSIP) shows a more indolent progression. Preclinical evidence of somatostatin receptor (SSTR) expression on fibroblasts in vitro and in lung fibrosis murine models, coupled with the longer survival of mice with fibrotic lungs treated with agents blocking SSTR, supports the hypothesis of imaging fibroblast activity in vivo by visualization of SSTR with (68)Ga-DOTANOC PET/CT. The aim of this study was to evaluate (68)Ga-DOTANOC PET/CT in patients with IPF and NSIP. METHODS Seven IPF patients and 7 NSIP patients were included in the study. (68)Ga-DOTANOC PET/CT and high-resolution CT (HRCT) were performed in all cases by following a standard procedure. PET/CT results were compared with disease sites and extent on HRCT. RESULTS In IPF, (68)Ga-DOTANOC uptake was peripheral, subpleural, and directly correlated with pathologic areas on HRCT (subpleural/reticular fibrosis, honeycombing). NSIP patients showed fainter tracer uptake, whereas corresponding HRCT showed areas of ground-glass opacity and rare fibrotic changes. Only IPF patients showed a linear correlation between maximal SUV and disease extent quantified both automatically (Q) (IPF: P = 0.002, R = 0.93) and using the visual score (Spearman ρ = 0.46, P = 0.0001). Q directly correlated with percentage carbon monoxide diffusing capacity in IPF (P = 0.03, R = 0.79) and NSIP (P = 0.05, R = 0.94), whereas maximal SUV did not present any correlation with percentage carbon monoxide diffusing capacity. CONCLUSION Our preliminary data show that (68)Ga-DOTANOC PET/CT demonstrates SSTR overexpression in IPF patients; this may prove interesting for the evaluation of novel treatments with somatostatin analogs.
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Affiliation(s)
- Valentina Ambrosini
- Nuclear Medicine, Azienda Ospedaliero-Universitaria di Bologna, S Orsola-Malpighi Hospital, Bologna, Italy.
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