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Erschienen in: Annals of Nuclear Medicine 1/2018

24.10.2017 | Short Communication

Low levels of PSMA expression limit the utility of 18F-DCFPyL PET/CT for imaging urothelial carcinoma

verfasst von: Scott P. Campbell, Alexander S. Baras, Mark W. Ball, Max Kates, Noah M. Hahn, Trinity J. Bivalacqua, Michael H. Johnson, Martin G. Pomper, Mohamad E. Allaf, Steven P. Rowe, Michael A. Gorin

Erschienen in: Annals of Nuclear Medicine | Ausgabe 1/2018

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Abstract

Objective

To explore the clinical utility of PSMA-targeted 18F-DCFPyL PET/CT in patients with metastatic urothelial carcinoma.

Methods

Three patients with metastatic urothelial carcinoma were imaged with 18F-DCFPyL PET/CT. All lesions with perceptible radiotracer uptake above background were considered positive. Maximum standardized uptake values were recorded for each detected lesion and findings on 18F-DCFPyL PET/CT were compared to those on conventional imaging studies. To further explore PSMA as a molecular target of urothelial carcinoma, RNA-sequencing data from The Cancer Genome Atlas were used to compare the relative expression of PSMA among cases of bladder cancer, prostate cancer, and clear cell renal cell carcinoma. Additionally, immunohistochemical staining for PSMA was performed on a biopsy specimen from one of the imaged patients.

Results

18F-DCFPyL PET/CT allowed for the detection of sites of urothelial carcinoma, albeit with low levels of radiotracer uptake. Analysis of RNA-sequencing data revealed that bladder cancer had significantly lower levels of PSMA expression than both prostate cancer and clear cell renal cell carcinoma. Consistent with this observation, immunohistochemical staining of tissue from one of the imaged patients demonstrated a low level of neovascularization and nearly absent PSMA expression.

Conclusion

The relatively scant expression of PSMA by urothelial carcinoma likely limits the utility of PSMA-targeted PET imaging of this malignancy. Future research efforts should focus on the development of other molecularly targeted imaging agents for urothelial carcinoma.
Literatur
1.
Zurück zum Zitat Clark PE, Agarwal N, Biagioli MC, et al. Bladder cancer. J Natl Compr Canc Netw. 2013;11(4):446–75.CrossRefPubMed Clark PE, Agarwal N, Biagioli MC, et al. Bladder cancer. J Natl Compr Canc Netw. 2013;11(4):446–75.CrossRefPubMed
2.
Zurück zum Zitat Mertens LS, Meijer RP, Meinhardt W, et al. Occult lymph node metastases in patients with carcinoma invading bladder muscle: incidence after neoadjuvant chemotherapy and cystectomy vs after cystectomy alone. BJU Int. 2014;114(1):67–74.CrossRefPubMed Mertens LS, Meijer RP, Meinhardt W, et al. Occult lymph node metastases in patients with carcinoma invading bladder muscle: incidence after neoadjuvant chemotherapy and cystectomy vs after cystectomy alone. BJU Int. 2014;114(1):67–74.CrossRefPubMed
3.
Zurück zum Zitat Zhang H, Xing W, Kang Q, Chen C, Wang L, Lu J. Diagnostic value of [18F] FDG-PET and PET/CT in urinary bladder cancer: a meta-analysis. Tumour Biol. 2015;36(5):3209–14.CrossRefPubMed Zhang H, Xing W, Kang Q, Chen C, Wang L, Lu J. Diagnostic value of [18F] FDG-PET and PET/CT in urinary bladder cancer: a meta-analysis. Tumour Biol. 2015;36(5):3209–14.CrossRefPubMed
4.
Zurück zum Zitat Soubra A, Hayward D, Dahm P. The diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography and computed tomography in staging bladder cancer: a single-institution study and a systematic review with meta-analysis. World J Urol. 2016;34(9):1229–37.CrossRefPubMed Soubra A, Hayward D, Dahm P. The diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography and computed tomography in staging bladder cancer: a single-institution study and a systematic review with meta-analysis. World J Urol. 2016;34(9):1229–37.CrossRefPubMed
5.
Zurück zum Zitat Pichler R, De Zordo T, Fritz J, et al. Pelvic lymph node staging by combined 18F-FDG-PET/CT imaging in bladder cancer prior to radical cystectomy. Clin Genitourin Cancer. 2017;15(3):e387-e395.CrossRefPubMed Pichler R, De Zordo T, Fritz J, et al. Pelvic lymph node staging by combined 18F-FDG-PET/CT imaging in bladder cancer prior to radical cystectomy. Clin Genitourin Cancer. 2017;15(3):e387-e395.CrossRefPubMed
6.
Zurück zum Zitat Vind-Kezunovic S, Bouchelouche K, Ipsen P, Høyer S, Bell C, Bjerggaard Jensen J. Detection of lymph node metastasis in patients with bladder cancer using maximum standardised uptake value and 18F-fluorodeoxyglucose positron emission tomography/computed tomography: results from a high-volume centre including long-term follow-up. Eur Urol Focus. 2017. doi:10.1016/j.euf.2017.06.005. Vind-Kezunovic S, Bouchelouche K, Ipsen P, Høyer S, Bell C, Bjerggaard Jensen J. Detection of lymph node metastasis in patients with bladder cancer using maximum standardised uptake value and 18F-fluorodeoxyglucose positron emission tomography/computed tomography: results from a high-volume centre including long-term follow-up. Eur Urol Focus. 2017. doi:10.​1016/​j.​euf.​2017.​06.​005.
7.
Zurück zum Zitat 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(10):2674–81.PubMed 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(10):2674–81.PubMed
8.
Zurück zum Zitat Chang SS, Reuter VE, Heston WD, Bander NH, Grauer LS, Gaudin PB. Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. Cancer Res. 1999;59(13):3192–8.PubMed Chang SS, Reuter VE, Heston WD, Bander NH, Grauer LS, Gaudin PB. Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. Cancer Res. 1999;59(13):3192–8.PubMed
9.
Zurück zum Zitat 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(2):385–90.CrossRef 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(2):385–90.CrossRef
10.
Zurück zum Zitat Gala JL, Loric S, Guiot Y, et al. Expression of prostate-specific membrane antigen in transitional cell carcinoma of the bladder: prognostic value? Clin Cancer Res. 2000;6(10):4049–54.PubMed Gala JL, Loric S, Guiot Y, et al. Expression of prostate-specific membrane antigen in transitional cell carcinoma of the bladder: prognostic value? Clin Cancer Res. 2000;6(10):4049–54.PubMed
11.
Zurück zum Zitat Maurer T, Eiber M, Schwaiger M, Gschwend JE. Current use of PSMA-PET in prostate cancer management. Nat Rev Urol. 2016;13(4):226–35.CrossRef Maurer T, Eiber M, Schwaiger M, Gschwend JE. Current use of PSMA-PET in prostate cancer management. Nat Rev Urol. 2016;13(4):226–35.CrossRef
12.
Zurück zum Zitat Rowe SP, Gorin MA, Hammers HJ, et al. Imaging of metastatic clear cell renal cell carcinoma with PSMA-targeted 18F-DCFPyL PET/CT. Ann Nucl Med. 2015;29(10):877–82.CrossRefPubMedPubMedCentral Rowe SP, Gorin MA, Hammers HJ, et al. Imaging of metastatic clear cell renal cell carcinoma with PSMA-targeted 18F-DCFPyL PET/CT. Ann Nucl Med. 2015;29(10):877–82.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Rowe SP, Gorin MA, Hammers HJ, Pomper MG, Allaf ME, Javadi MS. Detection of 18F-FDG PET/CT occult lesions with 18F-DCFPyL PET/CT in a patient with metastatic renal cell carcinoma. Clin Nucl Med. 2016;41(1):83–5.CrossRefPubMedPubMedCentral Rowe SP, Gorin MA, Hammers HJ, Pomper MG, Allaf ME, Javadi MS. Detection of 18F-FDG PET/CT occult lesions with 18F-DCFPyL PET/CT in a patient with metastatic renal cell carcinoma. Clin Nucl Med. 2016;41(1):83–5.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Rhee H, Blazak J, Tham CM, et al. Pilot study: use of gallium-68 PSMA PET for detection of metastatic lesions in patients with renal tumour. EJNMMI Res. 2016;6(1):76.CrossRefPubMedPubMedCentral Rhee H, Blazak J, Tham CM, et al. Pilot study: use of gallium-68 PSMA PET for detection of metastatic lesions in patients with renal tumour. EJNMMI Res. 2016;6(1):76.CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Gorin MA, Rowe SP, Hooper JE, et al. PSMA-Targeted 18F-DCFPyL PET/CT imaging of clear cell renal cell carcinoma: results from a rapid autopsy. Eur Urol. 2017;71(1):145–6.CrossRefPubMed Gorin MA, Rowe SP, Hooper JE, et al. PSMA-Targeted 18F-DCFPyL PET/CT imaging of clear cell renal cell carcinoma: results from a rapid autopsy. Eur Urol. 2017;71(1):145–6.CrossRefPubMed
16.
Zurück zum Zitat Sawicki LM, Buchbender C, Boos J, et al. Diagnostic potential of PET/CT using a 68Ga-labelled prostate-specific membrane antigen ligand in whole-body staging of renal cell carcinoma: initial experience. Eur J Nucl Med Mol Imaging. 2017;44(1):102–7.CrossRefPubMed Sawicki LM, Buchbender C, Boos J, et al. Diagnostic potential of PET/CT using a 68Ga-labelled prostate-specific membrane antigen ligand in whole-body staging of renal cell carcinoma: initial experience. Eur J Nucl Med Mol Imaging. 2017;44(1):102–7.CrossRefPubMed
17.
Zurück zum Zitat Sasikumar A, Joy A, Pillai MRA, Alex TM, Narayanan G. 68Ga-PSMA PET/CT in osteosarcoma in fibrous dysplasia. Clin Nucl Med. 2017;42(6):446–7.CrossRefPubMed Sasikumar A, Joy A, Pillai MRA, Alex TM, Narayanan G. 68Ga-PSMA PET/CT in osteosarcoma in fibrous dysplasia. Clin Nucl Med. 2017;42(6):446–7.CrossRefPubMed
18.
Zurück zum Zitat Sasikumar A, Joy A, Pillai MR, et al. Diagnostic value of 68Ga-PSMA-11 PET/CT imaging of brain tumors-preliminary analysis. Clin Nucl Med. 2017;42(1):e41-e48.CrossRefPubMed Sasikumar A, Joy A, Pillai MR, et al. Diagnostic value of 68Ga-PSMA-11 PET/CT imaging of brain tumors-preliminary analysis. Clin Nucl Med. 2017;42(1):e41-e48.CrossRefPubMed
19.
Zurück zum Zitat Sathekge M, Lengana T, Modiselle M, et al. 68Ga-PSMA-HBED-CC PET imaging in breast carcinoma patients. Eur J Nucl Med Mol Imaging. 2017;44(4):689–94.CrossRefPubMed Sathekge M, Lengana T, Modiselle M, et al. 68Ga-PSMA-HBED-CC PET imaging in breast carcinoma patients. Eur J Nucl Med Mol Imaging. 2017;44(4):689–94.CrossRefPubMed
20.
Zurück zum Zitat Sasikumar A, Joy A, Pillai M, Bindu S, Sudin SR. Ga-PSMA uptake in an incidentally detected gastrointestinal stromal tumor in a case of suspected carcinoma prostate. Clin Nucl Med. 2017;42(10):e447-e448.CrossRefPubMed Sasikumar A, Joy A, Pillai M, Bindu S, Sudin SR. Ga-PSMA uptake in an incidentally detected gastrointestinal stromal tumor in a case of suspected carcinoma prostate. Clin Nucl Med. 2017;42(10):e447-e448.CrossRefPubMed
21.
Zurück zum Zitat Sasikumar A, Joy A, Nanabala R, Pillai MR, Thomas B, Vikraman KR. 68Ga-PSMA PET/CT imaging in primary hepatocellular carcinoma. Eur J Nucl Med Mol Imaging. 2016;43(4):795–6.CrossRefPubMed Sasikumar A, Joy A, Nanabala R, Pillai MR, Thomas B, Vikraman KR. 68Ga-PSMA PET/CT imaging in primary hepatocellular carcinoma. Eur J Nucl Med Mol Imaging. 2016;43(4):795–6.CrossRefPubMed
22.
Zurück zum Zitat 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(10):1622–3.CrossRefPubMed 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(10):1622–3.CrossRefPubMed
23.
Zurück zum Zitat Pandit-Taskar N, O’Donoghue JA, Divgi CR, et al. Indium 111-labeled J591 anti-PSMA antibody for vascular targeted imaging in progressive solid tumors. EJNMMI Res. 2015;5:28.CrossRefPubMedPubMedCentral Pandit-Taskar N, O’Donoghue JA, Divgi CR, et al. Indium 111-labeled J591 anti-PSMA antibody for vascular targeted imaging in progressive solid tumors. EJNMMI Res. 2015;5:28.CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Milowsky MI, Nanus DM, Kostakoglu L, et al. Vascular targeted therapy with anti-prostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors. J Clin Oncol. 2007;25(5):540–7.CrossRefPubMed Milowsky MI, Nanus DM, Kostakoglu L, et al. Vascular targeted therapy with anti-prostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors. J Clin Oncol. 2007;25(5):540–7.CrossRefPubMed
25.
Zurück zum Zitat Gupta M, Choudhury PS, Gupta G, Gandhi J. Metastasis in urothelial carcinoma mimicking prostate cancer metastasis in Ga-68 prostate-specific membrane antigen positron emission tomography-computed tomography in a case of synchronous malignancy. Indian J Nucl Med. 2016;31(3):222–4.CrossRefPubMedPubMedCentral Gupta M, Choudhury PS, Gupta G, Gandhi J. Metastasis in urothelial carcinoma mimicking prostate cancer metastasis in Ga-68 prostate-specific membrane antigen positron emission tomography-computed tomography in a case of synchronous malignancy. Indian J Nucl Med. 2016;31(3):222–4.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Szabo Z, Mena E, Rowe SP, et al. Initial evaluation of [18F]DCFPyL for prostate-specific membrane antigen (PSMA)-targeted PET imaging of prostate cancer. Mol Imaging Biol. 2015;17(4):565 – 74.CrossRefPubMedPubMedCentral Szabo Z, Mena E, Rowe SP, et al. Initial evaluation of [18F]DCFPyL for prostate-specific membrane antigen (PSMA)-targeted PET imaging of prostate cancer. Mol Imaging Biol. 2015;17(4):565 – 74.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Rowe SP, Drzezga A, Neumaier B, et al. Prostate-specific membrane antigen-targeted radiohalogenated PET and therapeutic agents for prostate cancer. J Nucl Med. 2016;57(suppl 3):90S–96S. Rowe SP, Drzezga A, Neumaier B, et al. Prostate-specific membrane antigen-targeted radiohalogenated PET and therapeutic agents for prostate cancer. J Nucl Med. 2016;57(suppl 3):90S–96S.
28.
Zurück zum Zitat Rowe SP, Gorin MA, Salas Fragomeni RA, Drzezga A, Pomper MG. Clinical experience with 18F-labeled small molecule inhibitors of prostate-specific membrane antigen. PET Clin. 2017;12(2):235–41.CrossRefPubMed Rowe SP, Gorin MA, Salas Fragomeni RA, Drzezga A, Pomper MG. Clinical experience with 18F-labeled small molecule inhibitors of prostate-specific membrane antigen. PET Clin. 2017;12(2):235–41.CrossRefPubMed
29.
Zurück zum Zitat Dietlein M, Kobe C, Kuhnert G, et al. Comparison of [18F]DCFPyL and [68Ga]PSMA-HBED-CC for PSMA-PET imaging in patients with relapsed prostate cancer. Mol Imaging Biol. 2015;17(4):575 – 84.CrossRefPubMedPubMedCentral Dietlein M, Kobe C, Kuhnert G, et al. Comparison of [18F]DCFPyL and [68Ga]PSMA-HBED-CC for PSMA-PET imaging in patients with relapsed prostate cancer. Mol Imaging Biol. 2015;17(4):575 – 84.CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Dietlein F, Kobe C, Neubauer S, et al. PSA-stratified performance of 18F- and 68Ga-PSMA PET in patients with biochemical recurrence of prostate cancer. J Nucl Med. 2017;58(6):947–52.CrossRefPubMed Dietlein F, Kobe C, Neubauer S, et al. PSA-stratified performance of 18F- and 68Ga-PSMA PET in patients with biochemical recurrence of prostate cancer. J Nucl Med. 2017;58(6):947–52.CrossRefPubMed
31.
Zurück zum Zitat Li B, Dewey CN. RSEM: accurate transcript quantification from RNA-seq data with or without a reference genome. BMC Bioinf. 2011;12:323.CrossRef Li B, Dewey CN. RSEM: accurate transcript quantification from RNA-seq data with or without a reference genome. BMC Bioinf. 2011;12:323.CrossRef
32.
Metadaten
Titel
Low levels of PSMA expression limit the utility of 18F-DCFPyL PET/CT for imaging urothelial carcinoma
verfasst von
Scott P. Campbell
Alexander S. Baras
Mark W. Ball
Max Kates
Noah M. Hahn
Trinity J. Bivalacqua
Michael H. Johnson
Martin G. Pomper
Mohamad E. Allaf
Steven P. Rowe
Michael A. Gorin
Publikationsdatum
24.10.2017
Verlag
Springer Japan
Erschienen in
Annals of Nuclear Medicine / Ausgabe 1/2018
Print ISSN: 0914-7187
Elektronische ISSN: 1864-6433
DOI
https://doi.org/10.1007/s12149-017-1216-x

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