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DOI: 10.4103/wjnm.WJNM_78_19
An overview on prostate-specific membrane antigen uptake in malignancies other than prostate cancer: A pictorial essay
Abstract
Prostate-specific membrane antigen (PSMA) is a Type II transmembrane glycoprotein which is extremely overexpressed in prostate cancer epithelial cells. Recently, PSMA-targeted small molecule labeled with 68Ga and 99mTc allowed precise molecular imaging of prostate cancer and PSMA-targeted small molecule labeled with 177Lu leads to the development of radionuclide-targeted therapy of prostate cancer. Despite its name, it has been shown that PSMA has been expressed in several malignancies which can be due to significant neovascularization. Present pictorial assay reports the nonspecific tracer uptake in some malignancies during 68Ga-PSMA positron-emission tomography/computed tomography imaging and 99mTc-PSMA scintigraphy.
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Keywords
68Ga-prostate-specific membrane antigen positron-emission tomography/computed tomography - 99mTc-prostate-specific membrane antigen scintigraphy - prostate cancer - prostate-specific membrane antigen and nonspecific uptakeIntroduction
Prostate-specific membrane antigen (PSMA) is a Type II transmembrane glycoprotein which is extremely overexpressed in prostate cancer epithelial cells.[1] Higher tumor stage and grade, tumor dedifferentiation, hormone resistance, and metastatic disease lead to increase in overexpression of PSMA.[2] Although PSMA first was identified in the prostate gland, its expression in the duodenal epithelium, proximal tubule cells in the kidney, salivary glands, and tumor-associated vascular endothelium have been revealed in eventual histopathological studies.[3],[4],[5]
Recently, innovative development of PSMA-targeted small molecule labeled with 68Ga and 99mTc allowed precise molecular imaging of prostate cancer and PSMA-targeted small molecule labeled with 177Lu led to the development of radionuclide-targeted therapy of prostate cancer.
68Ga-PSMA positron-emission tomography (PET) since its first use in 2013 has revolutionized the management and imaging of patients with prostate cancer. Numerous studies have proved the high efficacy of 68Ga-PSMA in diagnosing, staging, follow-up, restaging, and evaluating treatment response.[6],[7],[8],[9]
Regarding the cost benefits and broader availability of single-photon emission computed tomography (CT) compared to PET, 99mTc-labeled small molecule inhibitor has been developed. The clinical evaluation and detection rate of 99mTc-PSMA in staging, recurrence, and treatment response of patients with prostate cancer have been evaluated in previous studies.[10],[11],[12],[13] Schmidkonz et al.[13] used 99mTc-MIP-1404 as a 99mTc-labeled PSMA inhibitor for the detection of prostate cancer with biochemical recurrence. Tracer-positive lesions were detected in 77% of patients, which indicated that this radiotracer has a high probability in the management of prostate cancer patients with biochemical recurrence. In another study, Reinfelder et al.[14] evaluated the detection efficacy of 99mTc-MIP-1404 in prostate cancer patients with biochemical recurrence. It has been reported that 70% of patients showed positive lesion which revealed that MIP-1404 is a promising radiotracer for the detection of prostate cancer lesions.
However, despite its name, in addition to prostate tissue, PSMA is physiologically expressed in a multiple number of nonprostatic malignancies because of PSMA mRNA transcripts and protein expression in the endothelium of tumor-related neovasculature, leading to potential pitfalls in the clinical use of PSMA-targeted imaging.[3],[4],[15] Nevertheless, PSMA expression in nonprostatic malignancies may prove beneficial in therapeutic and imaging targets for these conditions. [Table 1] represents malignancies other than prostate cancer which shows PSMA uptake in previous researches. In this pictorial assay, we reported a few nonprostatic malignancies cases, i.e., differentiated thyroid cancer, esophageal cancer, pancreaticobiliary adenocarcinoma, ureteral cancer, cholangiocarcinoma, pancreatoblastoma, hepatoblastoma, and carcinoma of unknown primary showing PSMA expression during 99mTc/177Lu-PSMA scintigraphy and 68Ga-PSMA PET imaging [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8].


















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Conclusion
Regarding the current literature, interpretation and reporting the PSMA scan in prostate cancer needs careful evaluation as its specificity is limited by some false-positive findings. These limitations may increase the diagnostic pitfalls and decrease the confidence of interpreting physicians. Nonspecific uptakes of 68Ga - labeled PSMA PET/CT and 99mTc/177Lu-PSMA scintigraphy for prostate imaging at the other malignancies apart from prostate cancer are being reported. Case reports have shown PSMA avidity in high-grade gliomas, lung cancer, breast cancer, multiple myeloma, and malignant melanoma due to the PSMA expression in the endothelial cells of the tumor neovasculature. The finding of PSMA expression in these malignancies may lead to radioligand-based therapeutic options.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflict of Interest
There are no conflicts of interest.
Financial support and sponsorship
Nil.
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References
- 1 Ahmadzadehfar H, Aryana K, Pirayesh E, Farzanehfar S, Assadi M, Fallahi B, et al. The Iranian Society of Nuclear Medicine practical guideline on radioligand therapy in metastatic castration-resistant prostate cancer using 177Lu-PSMA. Iran J of Nucl Med 2018;26:2-8.
- 2 DeMarzo AM, Nelson WG, Isaacs WB, Epstein JI. Pathological and molecular aspects of prostate cancer. Lancet 2003;361:955-64.
- 3 Malik D, Sood A, Mittal BR, Singh H, Basher RK, Shukla J, et al. Nonspecific Uptake of 68Ga-prostate-specific membrane antigen in diseases other than prostate malignancy on positron emission tomography/computed tomography imaging: A pictorial assay and review of literature. Indian J Nucl Med 2018;33:317-25.
- 4 Chang SS, O'Keefe DS, Bacich DJ, Reuter VE, Heston WD, Gaudin PB. Prostate-specific membrane antigen is produced in tumor-associated neovasculature. Clin Cancer Res 1999;5:2674-81.
- 5 Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res 1997;3:81-5.
- 6 Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, et al. The diagnostic value of PET/CT imaging with the 68Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2015;42:197-209.
- 7 Afshar-Oromieh A, Holland-Letz T, Giesel FL, Kratochwil C, Mier W, Haufe S, et al. Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: Evaluation in 1007 patients. Eur J Nucl Med Mol Imaging 2017;44:1258-68.
- 8 Hope TA, Truillet C, Ehman EC, Afshar-Oromieh A, Aggarwal R, Ryan CJ, et al. 68Ga-PSMA-11 PET imaging of response to androgen receptor inhibition:First human experience. J Nucl Med 2017;58:81-4.
- 9 Perera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG, et al. Sensitivity, specificity, and predictors of positive 68Ga-prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: A systematic review and meta-analysis. Eur Urol 2016;70:926-37.
- 10 Rathke H, Afshar AA, Giesel FL, Kremer C, Flechsig P, Haufe S, et al. Intra-individual comparison of Tc-99m-MDP bone scan and the PSMA-ligand Tc-99m-MIP-1427 in patients with osseous metastasized prostate cancer. J Nucl Med 2018;117.
- 11 Schmidkonz C, Cordes M, Beck M, Goetz TI, Schmidt D, Prante O, et al. SPECT/CT with the PSMA ligand 99mTc-MIP-1404 for whole-body primary staging of Patients with prostate cancer. Clin Nucl Med 2018;43:225-31.
- 12 Schmidkonz C, Cordes M, Beck M, Goetz TI, Schmidt D, Prante O, et al. Assessment of treatment response by 99mTc-MIP-1404 SPECT/CT: A pilot study in patients with metastatic prostate cancer. Clin Nucl Med 2018;43:e250-8.
- 13 Schmidkonz C, Hollweg C, Beck M, Reinfelder J, Goetz TI, Sanders JC, et al. 99mTc-MIP-1404-SPECT/CT for the detection of PSMA-positive lesions in 225 patients with biochemical recurrence of prostate cancer. Prostate 2018;78:54-63.
- 14 Reinfelder J, Kuwert T, Beck M, Sanders JC, Ritt P, Schmidkonz C, et al. First experience with SPECT/CT using a 99mTc-labeled inhibitor for prostate-specific membrane antigen in patients with biochemical recurrence of prostate cancer. Clin Nucl Med 2017;42:26-33.
- 15 Backhaus P, Noto B, Avramovic N, Grubert LS, Huss S, Bögemann M, et al. Targeting PSMA by radioligands in non-prostate disease-current status and future perspectives. Eur J Nucl Med Mol Imaging 2018;45:860-77.
- 16 Taywade SK, Damle NA, Bal C. PSMA expression in papillary thyroid carcinoma: Opening a new horizon in management of thyroid cancer? Clin Nucl Med 2016;41:e263-5.
- 17 Verma P, Malhotra G, Agrawal R, Sonavane S, Meshram V, Asopa RV. Evidence of prostate-specific membrane antigen expression in metastatic differentiated thyroid cancer using 68Ga-PSMA-HBED-CC PET/CT. Clin Nucl Med 2018;43:e265-8.
- 18 Bychkov A, Vutrapongwatana U, Tepmongkol S, Keelawat S. PSMA expression by microvasculature of thyroid tumors - Potential implications for PSMA theranostics. Sci Rep 2017;7:5202.
- 19 Sollini M, di Tommaso L, Kirienko M, Piombo C, Erreni M, Lania AG, et al. PSMA expression level predicts differentiated thyroid cancer aggressiveness and patient outcome. EJNMMI Res 2019;9:93.
- 20 Haffner MC, Laimer J, Chaux A, Schäfer G, Obrist P, Brunner A, et al. High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity. Mod Pathol 2012;25:1079-85.
- 21 Haffner MC, Kronberger IE, Ross JS, Sheehan CE, Zitt M, Mühlmann G, et al. Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers. Hum Pathol 2009;40:1754-61.
- 22 Wang HL, Wang SS, Song WH, Pan Y, Yu HP, Si TG, et al. Expression of prostate-specific membrane antigen in lung cancer cells and tumor neovasculature endothelial cells and its clinical significance. PLoS One 2015;10:e0125924.
- 23 Wernicke AG, Varma S, Greenwood EA, Christos PJ, Chao KS, Liu H, et al. Prostate-specific membrane antigen expression in tumor-associated vasculature of breast cancers. APMIS 2014;122:482-9.
- 24 Wernicke AG, Kim S, Liu H, Bander NH, Pirog EC. Prostate-specific membrane antigen (PSMA) expression in the neovasculature of gynecologic malignancies: Implications for PSMA-targeted therapy. Appl Immunohistochem Mol Morphol 2017;25:271-6.
- 25 Baccala A, Sercia L, Li J, Heston W, Zhou M. Expression of prostate-specific membrane antigen in tumor-associated neovasculature of renal neoplasms. Urology 2007;70:385-90.
- 26 Rhee H, Blazak J, Tham CM, Ng KL, Shepherd B, Lawson M, et al. Pilot study: Use of gallium-68 PSMA PET for detection of metastatic lesions in patients with renal tumour. EJNMMI Res 2016;6:76.
- 27 Samplaski MK, Heston W, Elson P, Magi-Galluzzi C, Hansel DE. Folate hydrolase (prostate-specific membrane [corrected] antigen) 1 expression in bladder cancer subtypes and associated tumor neovasculature. Mod Pathol 2011;24:1521-9.
- 28 Nomura N, Pastorino S, Jiang P, Lambert G, Crawford JR, Gymnopoulos M, et al. Prostate specific membrane antigen (PSMA) expression in primary gliomas and breast cancer brain metastases. Cancer Cell Int 2014;14:26.
- 29 Wernicke AG, Edgar MA, Lavi E, Liu H, Salerno P, Bander NH, et al. Prostate-specific membrane antigen as a potential novel vascular target for treatment of glioblastoma multiforme. Arch Pathol Lab Med 2011;135:1486-9.
- 30 Kanthan GL, Coyle L, Kneebone A, Schembri GP, Hsiao E. Follicular Lymphoma showing avid uptake on 68Ga PSMA-HBED-CC PET/CT. Clin Nucl Med 2016;41:500-1.
- 31 Sasikumar A, Joy A, Pillai MR, Nanabala R, Anees KM, Jayaprakash PG, et al. Diagnostic value of 68Ga PSMA-11 PET/CT imaging of brain tumors-preliminary analysis. Clin Nucl Med 2017;42:e41-8.
- 32 Sasikumar A, Joy A, Pillai MR, Nanabala R, Thomas B. 68Ga-PSMA PET/CT imaging in multiple myeloma. Clin Nucl Med 2017;42:e126-7.
- 33 Sasikumar A, Joy A, Nanabala R, Pillai MR, Thomas B, Vikraman KR. (68) Ga-PSMA PET/CT imaging in primary hepatocellular carcinoma. Eur J Nucl Med Mol Imaging 2016;43:795-6.
- 34 Sasikumar A, Joy A, Pillai MR, Alex TM, Narayanan G. 68Ga-PSMA PET/CT in osteosarcoma in fibrous dysplasia. Clin Nucl Med 2017;42:446-7.
- 35 Alipour R, Gupta S, Trethewey S. 68Ga-PSMA Uptake in combined hepatocellular cholangiocarcinoma with skeletal metastases. Clin Nucl Med 2017;42:e452-3.
- 36 Anconina R, Hod N, Levin D, Ezroh Kazap D, Lantsberg S. Incidental detection of metastatic malignant melanoma on 68Ga-prostate-specific membrane antigen PET/CT imaging: Correlative imaging With FDG PET/CT and review of the literature. Clin Nucl Med 2018;43:204-6.
- 37 Krishnaraju VS, Basher RK, Singh H, Singh SK, Bal A, Mittal BR. Incidental detection of Type B2 thymoma on 68Ga-labeled prostate-specific membrane antigen PET/CT imaging. Clin Nucl Med 2018;43:356-8.
- 38 Malik D, Kumar R, Mittal BR, Singh H, Bhattacharya A, Singh SK. 68Ga-labeled PSMA uptake in nonprostatic malignancies: Has the time come to remove “PS” From PSMA? Clin Nucl Med 2018;43:529-32.
- 39 Malik D, Kumar R, Mittal BR, Singh H, Bhattacharya A, Sood A, et al. 68Ga-labelled PSMA (prostate specific membrane antigen) expression in signet-ring cell gastric carcinoma. Eur J Nucl Med Mol Imaging 2018;45:1276-7.
- 40 Noto B, Weckesser M, Buerke B, Pixberg M, Avramovic N. Gastrointestinal stromal tumor showing intense tracer uptake on PSMA PET/CT. Clin Nucl Med 2017;42:200-2.
- 41 Stoykow C, Huber-Schumacher S, Almanasreh N, Jilg C, Ruf J. Strong PSMA radioligand uptake by rectal carcinoma: Who put the “S” in PSMA? Clin Nucl Med 2017;42:225-6.
- 42 Vamadevan S, Shetty D, Le K, Bui C, Mansberg R, Loh H. Prostate-specific membrane antigen (PSMA) avid pancreatic neuroendocrine tumor. Clin Nucl Med 2016;41:804-6.
- 43 Arora S, Damle NA, Aggarwal S, Passah A, Behera A, Arora G, et al. Prostate-specific membrane antigen expression in adrenocortical carcinoma on 68Ga-prostate-specific membrane antigen PET/CT. Clin Nucl Med 2018;43:449-51.
- 44 Froehner M, Kuithan F, Zöphel K, Heberling U, Laniado M, Wirth MP. Prostate-specific membrane antigen-targeted ligand positron emission tomography/computed tomography and immunohistochemical findings in a patient with synchronous metastatic penile and prostate cancer. Urology 2017;101:e5-6.
- 45 Verburg FA, Krohn T, Heinzel A, Mottaghy FM, Behrendt FF. First evidence of PSMA expression in differentiated thyroid cancer using [68Ga] PSMA-HBED-CC PET/CT. Eur J Nucl Med Mol Imaging 2015;42:1622-3.
- 46 Luster M, Weber T, Verburg FA. Differentiated thyroid cancer-personalized therapies to prevent overtreatment. Nat Rev Endocrinol 2014;10:563-74.
Address for correspondence
Publikationsverlauf
Eingereicht: 28. Oktober 2019
Angenommen: 28. Dezember 2019
Artikel online veröffentlicht:
19. April 2022
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References
- 1 Ahmadzadehfar H, Aryana K, Pirayesh E, Farzanehfar S, Assadi M, Fallahi B, et al. The Iranian Society of Nuclear Medicine practical guideline on radioligand therapy in metastatic castration-resistant prostate cancer using 177Lu-PSMA. Iran J of Nucl Med 2018;26:2-8.
- 2 DeMarzo AM, Nelson WG, Isaacs WB, Epstein JI. Pathological and molecular aspects of prostate cancer. Lancet 2003;361:955-64.
- 3 Malik D, Sood A, Mittal BR, Singh H, Basher RK, Shukla J, et al. Nonspecific Uptake of 68Ga-prostate-specific membrane antigen in diseases other than prostate malignancy on positron emission tomography/computed tomography imaging: A pictorial assay and review of literature. Indian J Nucl Med 2018;33:317-25.
- 4 Chang SS, O'Keefe DS, Bacich DJ, Reuter VE, Heston WD, Gaudin PB. Prostate-specific membrane antigen is produced in tumor-associated neovasculature. Clin Cancer Res 1999;5:2674-81.
- 5 Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res 1997;3:81-5.
- 6 Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, et al. The diagnostic value of PET/CT imaging with the 68Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2015;42:197-209.
- 7 Afshar-Oromieh A, Holland-Letz T, Giesel FL, Kratochwil C, Mier W, Haufe S, et al. Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: Evaluation in 1007 patients. Eur J Nucl Med Mol Imaging 2017;44:1258-68.
- 8 Hope TA, Truillet C, Ehman EC, Afshar-Oromieh A, Aggarwal R, Ryan CJ, et al. 68Ga-PSMA-11 PET imaging of response to androgen receptor inhibition:First human experience. J Nucl Med 2017;58:81-4.
- 9 Perera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG, et al. Sensitivity, specificity, and predictors of positive 68Ga-prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: A systematic review and meta-analysis. Eur Urol 2016;70:926-37.
- 10 Rathke H, Afshar AA, Giesel FL, Kremer C, Flechsig P, Haufe S, et al. Intra-individual comparison of Tc-99m-MDP bone scan and the PSMA-ligand Tc-99m-MIP-1427 in patients with osseous metastasized prostate cancer. J Nucl Med 2018;117.
- 11 Schmidkonz C, Cordes M, Beck M, Goetz TI, Schmidt D, Prante O, et al. SPECT/CT with the PSMA ligand 99mTc-MIP-1404 for whole-body primary staging of Patients with prostate cancer. Clin Nucl Med 2018;43:225-31.
- 12 Schmidkonz C, Cordes M, Beck M, Goetz TI, Schmidt D, Prante O, et al. Assessment of treatment response by 99mTc-MIP-1404 SPECT/CT: A pilot study in patients with metastatic prostate cancer. Clin Nucl Med 2018;43:e250-8.
- 13 Schmidkonz C, Hollweg C, Beck M, Reinfelder J, Goetz TI, Sanders JC, et al. 99mTc-MIP-1404-SPECT/CT for the detection of PSMA-positive lesions in 225 patients with biochemical recurrence of prostate cancer. Prostate 2018;78:54-63.
- 14 Reinfelder J, Kuwert T, Beck M, Sanders JC, Ritt P, Schmidkonz C, et al. First experience with SPECT/CT using a 99mTc-labeled inhibitor for prostate-specific membrane antigen in patients with biochemical recurrence of prostate cancer. Clin Nucl Med 2017;42:26-33.
- 15 Backhaus P, Noto B, Avramovic N, Grubert LS, Huss S, Bögemann M, et al. Targeting PSMA by radioligands in non-prostate disease-current status and future perspectives. Eur J Nucl Med Mol Imaging 2018;45:860-77.
- 16 Taywade SK, Damle NA, Bal C. PSMA expression in papillary thyroid carcinoma: Opening a new horizon in management of thyroid cancer? Clin Nucl Med 2016;41:e263-5.
- 17 Verma P, Malhotra G, Agrawal R, Sonavane S, Meshram V, Asopa RV. Evidence of prostate-specific membrane antigen expression in metastatic differentiated thyroid cancer using 68Ga-PSMA-HBED-CC PET/CT. Clin Nucl Med 2018;43:e265-8.
- 18 Bychkov A, Vutrapongwatana U, Tepmongkol S, Keelawat S. PSMA expression by microvasculature of thyroid tumors - Potential implications for PSMA theranostics. Sci Rep 2017;7:5202.
- 19 Sollini M, di Tommaso L, Kirienko M, Piombo C, Erreni M, Lania AG, et al. PSMA expression level predicts differentiated thyroid cancer aggressiveness and patient outcome. EJNMMI Res 2019;9:93.
- 20 Haffner MC, Laimer J, Chaux A, Schäfer G, Obrist P, Brunner A, et al. High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity. Mod Pathol 2012;25:1079-85.
- 21 Haffner MC, Kronberger IE, Ross JS, Sheehan CE, Zitt M, Mühlmann G, et al. Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers. Hum Pathol 2009;40:1754-61.
- 22 Wang HL, Wang SS, Song WH, Pan Y, Yu HP, Si TG, et al. Expression of prostate-specific membrane antigen in lung cancer cells and tumor neovasculature endothelial cells and its clinical significance. PLoS One 2015;10:e0125924.
- 23 Wernicke AG, Varma S, Greenwood EA, Christos PJ, Chao KS, Liu H, et al. Prostate-specific membrane antigen expression in tumor-associated vasculature of breast cancers. APMIS 2014;122:482-9.
- 24 Wernicke AG, Kim S, Liu H, Bander NH, Pirog EC. Prostate-specific membrane antigen (PSMA) expression in the neovasculature of gynecologic malignancies: Implications for PSMA-targeted therapy. Appl Immunohistochem Mol Morphol 2017;25:271-6.
- 25 Baccala A, Sercia L, Li J, Heston W, Zhou M. Expression of prostate-specific membrane antigen in tumor-associated neovasculature of renal neoplasms. Urology 2007;70:385-90.
- 26 Rhee H, Blazak J, Tham CM, Ng KL, Shepherd B, Lawson M, et al. Pilot study: Use of gallium-68 PSMA PET for detection of metastatic lesions in patients with renal tumour. EJNMMI Res 2016;6:76.
- 27 Samplaski MK, Heston W, Elson P, Magi-Galluzzi C, Hansel DE. Folate hydrolase (prostate-specific membrane [corrected] antigen) 1 expression in bladder cancer subtypes and associated tumor neovasculature. Mod Pathol 2011;24:1521-9.
- 28 Nomura N, Pastorino S, Jiang P, Lambert G, Crawford JR, Gymnopoulos M, et al. Prostate specific membrane antigen (PSMA) expression in primary gliomas and breast cancer brain metastases. Cancer Cell Int 2014;14:26.
- 29 Wernicke AG, Edgar MA, Lavi E, Liu H, Salerno P, Bander NH, et al. Prostate-specific membrane antigen as a potential novel vascular target for treatment of glioblastoma multiforme. Arch Pathol Lab Med 2011;135:1486-9.
- 30 Kanthan GL, Coyle L, Kneebone A, Schembri GP, Hsiao E. Follicular Lymphoma showing avid uptake on 68Ga PSMA-HBED-CC PET/CT. Clin Nucl Med 2016;41:500-1.
- 31 Sasikumar A, Joy A, Pillai MR, Nanabala R, Anees KM, Jayaprakash PG, et al. Diagnostic value of 68Ga PSMA-11 PET/CT imaging of brain tumors-preliminary analysis. Clin Nucl Med 2017;42:e41-8.
- 32 Sasikumar A, Joy A, Pillai MR, Nanabala R, Thomas B. 68Ga-PSMA PET/CT imaging in multiple myeloma. Clin Nucl Med 2017;42:e126-7.
- 33 Sasikumar A, Joy A, Nanabala R, Pillai MR, Thomas B, Vikraman KR. (68) Ga-PSMA PET/CT imaging in primary hepatocellular carcinoma. Eur J Nucl Med Mol Imaging 2016;43:795-6.
- 34 Sasikumar A, Joy A, Pillai MR, Alex TM, Narayanan G. 68Ga-PSMA PET/CT in osteosarcoma in fibrous dysplasia. Clin Nucl Med 2017;42:446-7.
- 35 Alipour R, Gupta S, Trethewey S. 68Ga-PSMA Uptake in combined hepatocellular cholangiocarcinoma with skeletal metastases. Clin Nucl Med 2017;42:e452-3.
- 36 Anconina R, Hod N, Levin D, Ezroh Kazap D, Lantsberg S. Incidental detection of metastatic malignant melanoma on 68Ga-prostate-specific membrane antigen PET/CT imaging: Correlative imaging With FDG PET/CT and review of the literature. Clin Nucl Med 2018;43:204-6.
- 37 Krishnaraju VS, Basher RK, Singh H, Singh SK, Bal A, Mittal BR. Incidental detection of Type B2 thymoma on 68Ga-labeled prostate-specific membrane antigen PET/CT imaging. Clin Nucl Med 2018;43:356-8.
- 38 Malik D, Kumar R, Mittal BR, Singh H, Bhattacharya A, Singh SK. 68Ga-labeled PSMA uptake in nonprostatic malignancies: Has the time come to remove “PS” From PSMA? Clin Nucl Med 2018;43:529-32.
- 39 Malik D, Kumar R, Mittal BR, Singh H, Bhattacharya A, Sood A, et al. 68Ga-labelled PSMA (prostate specific membrane antigen) expression in signet-ring cell gastric carcinoma. Eur J Nucl Med Mol Imaging 2018;45:1276-7.
- 40 Noto B, Weckesser M, Buerke B, Pixberg M, Avramovic N. Gastrointestinal stromal tumor showing intense tracer uptake on PSMA PET/CT. Clin Nucl Med 2017;42:200-2.
- 41 Stoykow C, Huber-Schumacher S, Almanasreh N, Jilg C, Ruf J. Strong PSMA radioligand uptake by rectal carcinoma: Who put the “S” in PSMA? Clin Nucl Med 2017;42:225-6.
- 42 Vamadevan S, Shetty D, Le K, Bui C, Mansberg R, Loh H. Prostate-specific membrane antigen (PSMA) avid pancreatic neuroendocrine tumor. Clin Nucl Med 2016;41:804-6.
- 43 Arora S, Damle NA, Aggarwal S, Passah A, Behera A, Arora G, et al. Prostate-specific membrane antigen expression in adrenocortical carcinoma on 68Ga-prostate-specific membrane antigen PET/CT. Clin Nucl Med 2018;43:449-51.
- 44 Froehner M, Kuithan F, Zöphel K, Heberling U, Laniado M, Wirth MP. Prostate-specific membrane antigen-targeted ligand positron emission tomography/computed tomography and immunohistochemical findings in a patient with synchronous metastatic penile and prostate cancer. Urology 2017;101:e5-6.
- 45 Verburg FA, Krohn T, Heinzel A, Mottaghy FM, Behrendt FF. First evidence of PSMA expression in differentiated thyroid cancer using [68Ga] PSMA-HBED-CC PET/CT. Eur J Nucl Med Mol Imaging 2015;42:1622-3.
- 46 Luster M, Weber T, Verburg FA. Differentiated thyroid cancer-personalized therapies to prevent overtreatment. Nat Rev Endocrinol 2014;10:563-74.

















