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Badrane I, Castello A, Brunelli M, Cittanti C, Adamantiadis S, Bagni I, Mindicini N, Lancia F, Castellani M, Uccelli L, Bartolomei M, Urso L. Atypical Metastases from Prostate Cancer: Alpha-Methylacyl-Coenzyme A Racemase (AMACR) as a Potential Molecular Target in Prostate-Specific Membrane Antigen-Negative Prostate Adenocarcinoma. Biomolecules 2024; 15:17. [PMID: 39858412 PMCID: PMC11762331 DOI: 10.3390/biom15010017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 11/25/2024] [Accepted: 12/25/2024] [Indexed: 01/27/2025] Open
Abstract
Prostate cancer (PCa) is a high-prevalence disease usually characterized by metastatic spread to the pelvic lymph nodes and bones and the development of visceral metastases only in the late stages of disease. Positron Emission Tomography (PET) plays a key role in the detection of PCa metastases. Several PET radiotracers are used in PCa patients according to the stage and pathological features of the disease, in particular 68Ga/18F-prostate-specific membrane antigen (PSMA) ligands. Moreover, 2-deoxy-2-[18F]fluoro-D-glucose 18F-FDG PET usually shows metastases in the late stages of disease, when dedifferentiated neoplastic clones lose PSMA expression. In some cases, PCa patients may present atypical sites of metastases, with uncommon appearance at PET imaging with different radiotracers. We present the case of a patient with biochemical recurrence of PCa (ISUP Grade Group IV; PSA 4.7 ng/mL) showing atypical sites of metastases (the testis and multiple lung nodules) with absent PSMA expression and high [18F]FDG avidity. The patient showed diffuse positivity to alpha-methylacyl-coenzyme A racemase (AMACR). Moreover, a literature review was performed by collecting cases of PCa patients with atypical metastatic spread detected via PET imaging, with the aim of highlighting the relationship between atypical sites of metastases, imaging presentation, and pathology findings.
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Affiliation(s)
- Ilham Badrane
- Department of Translational Medicine, University of Ferrara, Via Aldo Moro 8, 44124 Ferrara, Italy; (I.B.); (S.A.); (L.U.); (L.U.)
- Nuclear Medicine Unit, Onco-Hematology Department, University Hospital of Ferrara, 44124 Ferrara, Italy;
| | - Angelo Castello
- Nuclear Medicine Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (A.C.); (M.C.)
| | - Matteo Brunelli
- Department of Pathology and Diagnostic Health, University of Verona, 37100 Verona, Italy;
| | - Corrado Cittanti
- Department of Translational Medicine, University of Ferrara, Via Aldo Moro 8, 44124 Ferrara, Italy; (I.B.); (S.A.); (L.U.); (L.U.)
- Nuclear Medicine Unit, Onco-Hematology Department, University Hospital of Ferrara, 44124 Ferrara, Italy;
| | - Sara Adamantiadis
- Department of Translational Medicine, University of Ferrara, Via Aldo Moro 8, 44124 Ferrara, Italy; (I.B.); (S.A.); (L.U.); (L.U.)
- Nuclear Medicine Unit, Onco-Hematology Department, University Hospital of Ferrara, 44124 Ferrara, Italy;
| | - Ilaria Bagni
- Anatomic Pathology Unit, University Hospital of Ferrara, 44124 Ferrara, Italy;
| | - Noemi Mindicini
- Oncology Unit, University Hospital of Ferrara, 44124 Ferrara, Italy; (N.M.); (F.L.)
| | - Federica Lancia
- Oncology Unit, University Hospital of Ferrara, 44124 Ferrara, Italy; (N.M.); (F.L.)
| | - Massimo Castellani
- Nuclear Medicine Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (A.C.); (M.C.)
| | - Licia Uccelli
- Department of Translational Medicine, University of Ferrara, Via Aldo Moro 8, 44124 Ferrara, Italy; (I.B.); (S.A.); (L.U.); (L.U.)
- Nuclear Medicine Unit, Onco-Hematology Department, University Hospital of Ferrara, 44124 Ferrara, Italy;
| | - Mirco Bartolomei
- Nuclear Medicine Unit, Onco-Hematology Department, University Hospital of Ferrara, 44124 Ferrara, Italy;
| | - Luca Urso
- Department of Translational Medicine, University of Ferrara, Via Aldo Moro 8, 44124 Ferrara, Italy; (I.B.); (S.A.); (L.U.); (L.U.)
- Nuclear Medicine Unit, Onco-Hematology Department, University Hospital of Ferrara, 44124 Ferrara, Italy;
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Okamoto T. Malignant biliary obstruction due to metastatic non-hepato-pancreato-biliary cancer. World J Gastroenterol 2022; 28:985-1008. [PMID: 35431494 PMCID: PMC8968522 DOI: 10.3748/wjg.v28.i10.985] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 07/03/2021] [Accepted: 02/16/2022] [Indexed: 02/06/2023] Open
Abstract
Malignant biliary obstruction generally results from primary malignancies of the pancreatic head, bile duct, gallbladder, liver, and ampulla of Vater. Metastatic lesions from other primaries to these organs or nearby lymph nodes are rarer causes of biliary obstruction. The most common primaries include renal cancer, lung cancer, gastric cancer, colorectal cancer, breast cancer, lymphoma, and melanoma. They may be difficult to differentiate from primary hepato-pancreato-biliary cancer based on imaging studies, or even on biopsy. There is also no consensus on the optimal method of treatment, including the feasibility and effectiveness of endoscopic intervention or surgery. A thorough review of the literature on pancreato-biliary metastases and malignant biliary obstruction due to metastatic non-hepato-pancreato-biliary cancer is presented. The diagnostic modality and clinical characteristics may differ significantly depending on the type of primary cancer. Different primaries also cause malignant biliary obstruction in different ways, including direct invasion, pancreatic or biliary metastasis, hilar lymph node metastasis, liver metastasis, and peritoneal carcinomatosis. Metastasectomy may hold promise for some types of pancreato-biliary metastases. This review aims to elucidate the current knowledge in this area, which has received sparse attention in the past. The aging population, advances in diagnostic imaging, and improved treatment options may lead to an increase in these rare occurrences going forward.
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Affiliation(s)
- Takeshi Okamoto
- Department of Gastroenterology, St. Luke’s International Hospital, Chuo-ku 104-8560, Tokyo, Japan
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Atypical Metastases in the Abdomen and Pelvis From Biochemically Recurrent Prostate Cancer: 11C-Choline PET/CT Imaging With Multimodality Correlation. AJR Am J Roentgenol 2021; 218:141-150. [PMID: 34346785 DOI: 10.2214/ajr.21.26426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
PET imaging with targeted radiotracers has become integral for mapping the location and burden of recurrent disease in patients with biochemical recurrence (BCR) of prostate cancer (PCa). PET with 11C-choline is part of the National Comprehensive Cancer Network and European Association of Urology guidelines for evaluation of BCR. With advances in PET technology, increasing use of targeted radiotracers, and improved survival of patients with BCR due to novel therapeutics, atypical sites of metastases are being increasingly encountered, challenging the conventional view that PCa rarely metastasizes beyond bones or lymph nodes. We describe such atypical metastases in the abdomen and pelvis on 11C-choline PET (including in the liver, pancreas, genital tract, urinary tract, peritoneum, and abdominal wall, as well as perineural spread), presenting multimodality imaging features and relevant imaging pitfalls. Given atypical metastases' inconsistent relationship with serum PSA and non-specific presenting symptoms, they are often first detected on imaging. Awareness of their imaging features is important as their detection impacts clinical management, patient counseling, prognosis, and clinical trial eligibility. Such awareness is particularly critical as the role of radiologists in the imaging and management of BCR will continue to increase given the expanding regulatory approvals of other targeted and theranostic radiotracers.
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Isolated Pancreatic Metastasis From Squamous Cell Lung Cancer Mimicking Primary Pancreatic Ductal Adenocarcinoma on FDG PET/CT. Clin Nucl Med 2020; 45:420-422. [PMID: 32149802 DOI: 10.1097/rlu.0000000000002986] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Isolated pancreatic metastasis from lung cancer is rare. We present a case of isolated pancreatic metastasis from squamous cell lung cancer. The pancreatic tumor showed hypovascularity on enhanced MRI and intense FDG uptake on FDG PET/CT mimicking primary pancreatic ductal adenocarcinoma. This case indicates pancreatic metastasis should be considered as a differential diagnosis in patients with a history of extrapancreatic cancer and hypermetabolic pancreatic lesion.
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Concurrent Pancreatic Metastasis From Lung Adenocarcinoma and Primary Cholangiocarcinoma on FDG PET/CT Imaging. Clin Nucl Med 2019; 44:426-428. [PMID: 30762824 DOI: 10.1097/rlu.0000000000002496] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
A 67-year-old man with a history of left upper lobe resection of poorly differentiated adenocarcinoma 1 year ago underwent FDG PET/CT for restaging. The images demonstrated a round cystic lesion with peripheral FDG uptake and centrally photopenic region. Additional focus of increased activity was detected in the left lobe of the liver. The patient underwent the Whipple and partial hepatectomy. The surgical pathology demonstrated concurrently the metastasis to the pancreas from the lung adenocarcinoma and a primary moderately differentiated cholangiocarcinoma.
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Hu S, Zhang J, Zuo C, Cheng C, Liu Q, Sun G. (18)F-FDG-PET/CT findings in pancreatic metastasis. LA RADIOLOGIA MEDICA 2015; 120:887-898. [PMID: 25795439 DOI: 10.1007/s11547-014-0473-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/27/2014] [Accepted: 09/14/2014] [Indexed: 12/29/2022]
Abstract
PURPOSE This study aimed to evaluate the fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) findings and pattern of FDG uptake in pancreatic metastases. MATERIALS AND METHODS A total of 19 consecutive patients (26 lesions) with histologically or clinically confirmed pancreatic metastases who had undergone (18)F-FDG-PET/CT were enrolled in this retrospective study. Among the 19 patients, 14 patients underwent abdominal contrast-enhanced CT (ceCT). The location, size and FDG uptake patterns of the pancreatic lesions were recorded. Metabolic activity by means of maximum standardised uptake value (SUVmax) was measured by drawing regions of interest at the site of pancreatic lesions. Twenty pancreatic cancer patients were included in this study as comparative data analysis. The difference of SUVmax between pancreatic metastases and primary pancreatic cancer were compared using the Mann-Whitney U test. P < 0.05 was considered significant. RESULTS Three different patterns of FDG uptake could be distinguished in the pancreatic metastatic lesions, including focal nodule or mass, multiple foci and segmental lesion with high FDG uptake. The average SUVmax in pancreatic metastases was 7.8 ± 6.9 versus 7.4 ± 3.9 in primary pancreatic cancer (P = 0.987 > 0.05). Four intrapancreatic isodense nodules in three patients were undetected on ceCT. CONCLUSION The described patterns of FDG uptake findings may be helpful for a better characterisation of pancreatic metastases although semiquantitative analysis using SUVmax could not be used as a criterion for differentiating pancreatic metastases from primary pancreatic cancer. FDG-PET/CT has also an advantage in detecting unsuspected pancreatic metastases which cannot be detected by ceCT imaging. Thus, it is a useful adjunct to the described features on CT.
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Affiliation(s)
- Shengping Hu
- Department of Nuclear Medicine, Changhai Hospital of Second Military Medical University, 168 Changhai Road, YangPu, Shanghai, 200433, China.
| | - Jian Zhang
- Department of Nuclear Medicine, Changhai Hospital of Second Military Medical University, 168 Changhai Road, YangPu, Shanghai, 200433, China.
| | - Changjing Zuo
- Department of Nuclear Medicine, Changhai Hospital of Second Military Medical University, 168 Changhai Road, YangPu, Shanghai, 200433, China.
| | - Chao Cheng
- Department of Nuclear Medicine, Changhai Hospital of Second Military Medical University, 168 Changhai Road, YangPu, Shanghai, 200433, China.
| | - Qinghua Liu
- Department of Nuclear Medicine, Changhai Hospital of Second Military Medical University, 168 Changhai Road, YangPu, Shanghai, 200433, China.
| | - Gaofeng Sun
- Department of Nuclear Medicine, Changhai Hospital of Second Military Medical University, 168 Changhai Road, YangPu, Shanghai, 200433, China.
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Hall NC, Nichols SD, Povoski SP, James IAO, Wright CL, Harris R, Schmidt CR, Muscarella P, Latchana N, Martin EW, Ellison EC. Intraoperative Use of a Portable Large Field of View Gamma Camera and Handheld Gamma Detection Probe for Radioguided Localization and Prediction of Complete Surgical Resection of Gastrinoma: Proof of Concept. J Am Coll Surg 2015. [PMID: 26206636 DOI: 10.1016/j.jamcollsurg.2015.03.047] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND Surgical management of Zollinger-Ellison syndrome (ZES) relies on localization and resection of all tumor foci. We describe the benefit of combined intraoperative use of a portable large field of view gamma camera (LFOVGC) and a handheld gamma detection probe (HGDP) for indium-111 ((111)In)-pentetreotide radioguided localization and confirmation of gastrinoma resection in ZES. STUDY DESIGN Five patients (6 cases) with (111)In-pentetreotide-avid ZES were evaluated. Patients were injected with (111)In-pentetreotide for diagnostic imaging the day before surgery. Intraoperatively, an HGDP and LFOVGC were used to localize (111)In-pentetreotide-avid lesions, guide resection, assess specimens for (111)In-pentetreotide activity, and to verify lack of abnormal post-resection surgical field activity. RESULTS Large field of view gamma camera imaging and HGDP-assisted detection were helpful for localization and guided resection of tumor and removal of (111)In-pentetreotide-avid tumor foci in all cases. In 3 of 5 patients (3 of 6 cases), these techniques led to detection and resection of additional tumor foci beyond those detected by standard surgical techniques. The (111)In-pentetreotide-positive or-negative specimens correlated with neuroendocrine tumors or benign pathology, respectively. In one patient with mild residual focal activity on post-resection portable LFOVGC imaging, thought to be artifact, had recurrence of disease in the same area 5 months after surgery. CONCLUSIONS Real-time LFOVGC imaging and HGDP use for surgical management of gastrinoma improve success of localizing and resecting all neuroendocrine tumor-positive tumor foci, providing instantaneous navigational feedback. This approach holds potential for improving long-term patient outcomes in patients with ZES.
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Affiliation(s)
- Nathan C Hall
- Department of Radiology, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH; Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA.
| | - Shawnn D Nichols
- Department of Surgery, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH; Department of Surgery, San Antonio Military Medical Center, Fort Sam Houston, TX
| | - Stephen P Povoski
- Department of Surgery, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH
| | - Iyore A O James
- Department of Surgery, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH
| | - Chadwick L Wright
- Department of Radiology, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH
| | - Randall Harris
- Division of Epidemiology, The Ohio State University, Wexner Medical Center, Columbus, OH
| | - Carl R Schmidt
- Department of Surgery, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH
| | - Peter Muscarella
- Department of Surgery, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH
| | - Nicholas Latchana
- Department of Surgery, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH
| | - Edward W Martin
- Department of Surgery, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH
| | - E Christopher Ellison
- Department of Surgery, College of Public Health, The Ohio State University, Wexner Medical Center, Columbus, OH
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Maines F, Caffo O, Veccia A, Galligioni E. Gastrointestinal metastases from prostate cancer: a review of the literature. Future Oncol 2015; 11:691-702. [DOI: 10.2217/fon.14.253] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
ABSTRACT The availability of active new drugs for the treatment of advanced castration-resistant prostate cancer has significantly prolonged overall survival, thus changing the natural history of the disease and raising the likelihood of observing metastases in atypical sites. This review of the literature describes the frequency, clinical-pathological features and presenting symptoms of non-liver gastrointestinal metastases (GIm) from prostate cancer. Its purpose is to increase clinical awareness of the increasing incidence of such GIm, contributing to the early detection, accurate diagnosis and, when feasible, appropriate management.
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Affiliation(s)
- Francesca Maines
- Medical Oncology Department, S Chiara Hospital, Largo Medaglie d'Oro 1, 38100 Trento, Italy
| | - Orazio Caffo
- Medical Oncology Department, S Chiara Hospital, Largo Medaglie d'Oro 1, 38100 Trento, Italy
| | - Antonello Veccia
- Medical Oncology Department, S Chiara Hospital, Largo Medaglie d'Oro 1, 38100 Trento, Italy
| | - Enzo Galligioni
- Medical Oncology Department, S Chiara Hospital, Largo Medaglie d'Oro 1, 38100 Trento, Italy
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Wang W, Stroehlein JR, Landon G, Ross WA. Prostate Cancer Metastatic to the Pancreas. J Clin Oncol 2013; 31:e367-9. [DOI: 10.1200/jco.2012.45.1427] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Wei Wang
- University of Texas MD Anderson Cancer Center, Houston, TX
| | | | - Gene Landon
- University of Texas MD Anderson Cancer Center, Houston, TX
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Current World Literature. Curr Opin Support Palliat Care 2012; 6:402-16. [DOI: 10.1097/spc.0b013e3283573126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Tan M, Burden-Gulley SM, Li W, Wu X, Lindner D, Brady-Kalnay SM, Gulani V, Lu ZR. MR molecular imaging of prostate cancer with a peptide-targeted contrast agent in a mouse orthotopic prostate cancer model. Pharm Res 2011; 29:953-60. [PMID: 22139536 DOI: 10.1007/s11095-011-0635-y] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2011] [Accepted: 11/21/2011] [Indexed: 02/01/2023]
Abstract
PURPOSE To study the effectiveness of a peptide targeted nanoglobular Gd-DOTA complexes for MR molecular imaging of prostate cancer in a mouse orthotopic PC-3 prostate cancer model. METHODS A CLT1 (CGLIIQKNEC) peptide-targeted generation 2 nanoglobular Gd-DOTA monoamide conjugate [CLT1-G2-(Gd-DOTA)] was used for imaging fibrin-fibronectin complexes in prostate tumor using a non-specific peptide KAREC modified conjugate, KAREC-G2-(Gd-DOTA) as a control. Cy5 conjugates of CLT1 and KAREC were synthesized for binding studies. Orthotopic PC-3 prostate tumors were established in the prostate of athymic male nude mice. MRI study was performed on a Bruker 7T small animal MRI system. RESULTS CLT1 peptide showed specific binding in the prostate tumor with no binding in normal tissues. The control peptide had little binding in normal and tumor tissues. CLT1-G2-(Gd-DOTA) resulted in stronger contrast enhancement in tumor tissue than KAREC-G2-(Gd-DOTA). CLT1-G2-(Gd-DOTA) generated ~100% increase in contrast-to-noise ratio (CNR) in the tumor compared to precontrast CNR at 1 min post-injection, while KAREC-G2-(Gd-DOTA) resulted in 8% increase. CONCLUSION CLT1-G2-(Gd-DOTA) is a promising molecular MRI contrast agent for fibrin-fibronectin complexes in tumor stroma. It has potential for diagnosis and assessing prognosis of malignant tumors with MRI.
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Affiliation(s)
- Mingqian Tan
- Department of Biomedical Engineering, Case Western Reserve University, Wickenden Building, Room 427, 10900 Euclid Avenue, Cleveland, Ohio 44106-7207, USA
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