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Published in: EJNMMI Research 1/2019

Open Access 01-12-2019 | Prostate Cancer | Original research

Comparison of the radiolabeled PSMA-inhibitor 111In-PSMA-617 and the radiolabeled GRP-R antagonist 111In-RM2 in primary prostate cancer samples

Authors: Romain Schollhammer, Henri De Clermont Gallerande, Mokrane Yacoub, Marie-Laure Quintyn Ranty, Nicole Barthe, Delphine Vimont, Elif Hindié, Philippe Fernandez, Clément Morgat

Published in: EJNMMI Research | Issue 1/2019

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Abstract

Purpose

Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRP-R) are expressed in prostate cancer and can be targeted with radiolabeled inhibitors and antagonists. Their performances for the initial characterization of prostatic tumors have been barely evaluated but never compared. We aimed to gather comparative preclinical data of the role of PSMA and GRP-R targeting in prostate cancer.

Procedures

We retrospectively studied 20 frozen prostatectomy samples with various metastatic risks of the D’Amico classification. Tissue samples were investigated by tissular microimaging using the radiolabeled PSMA inhibitor 111In-PSMA-617 and the radiolabeled GRP-R antagonist 111In-RM2. Bindings of the two radiopharmaceuticals were compared to histology and clinico-biological data (Gleason score, PSA values, metastatic risks).

Results

Binding of 111In-PSMA-617 was high whatever the metastatic risk (p = 0.665), Gleason score (p = 0.555), or PSA value (p = 0.404) while 111In-RM2 exhibited a significantly higher binding in the low metastatic risk group (p = 0.046), in the low PSA value group (p = 0.001), and in samples with Gleason 6 score (p = 0.006).

Conclusion

PSMA and GRP-R based imaging might have complementary performances for the initial characterization of prostatic tumors. Prospective clinical studies comparing the two tracers in this setting are needed.
Literature
1.
go back to reference Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67:7–30.CrossRef Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67:7–30.CrossRef
2.
go back to reference Afshar-Oromieh A, Zechmann CM, Malcher A, et al. Comparison of PET imaging with a 68Ga-labelled PSMA ligand and 18F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2014;41:11–20.CrossRef Afshar-Oromieh A, Zechmann CM, Malcher A, et al. Comparison of PET imaging with a 68Ga-labelled PSMA ligand and 18F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2014;41:11–20.CrossRef
3.
go back to reference Eder M, Schäfer M, Bauder-Wüst U, et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem. 2012;23:688–97.CrossRef Eder M, Schäfer M, Bauder-Wüst U, et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem. 2012;23:688–97.CrossRef
4.
go back to reference Morgat C, Mishra AK, Varshney R, et al. Targeting neuropeptide receptors for cancer imaging and therapy: perspectives with bombesin, neurotensin, and neuropeptide-Y receptors. J Nucl Med. 2014;55:1650–7.CrossRef Morgat C, Mishra AK, Varshney R, et al. Targeting neuropeptide receptors for cancer imaging and therapy: perspectives with bombesin, neurotensin, and neuropeptide-Y receptors. J Nucl Med. 2014;55:1650–7.CrossRef
5.
go back to reference Schwarzenboeck SM, Rauscher I, Bluemel C, et al. PSMA ligands for PET imaging of prostate cancer. J Nucl Med. 2017;58:1545–52.CrossRef Schwarzenboeck SM, Rauscher I, Bluemel C, et al. PSMA ligands for PET imaging of prostate cancer. J Nucl Med. 2017;58:1545–52.CrossRef
6.
go back to reference Uprimny C, Kroiss AS, Decristoforo C, et al. 68Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour. Eur J Nucl Med Mol Imaging. 2017;44:941–9.CrossRef Uprimny C, Kroiss AS, Decristoforo C, et al. 68Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour. Eur J Nucl Med Mol Imaging. 2017;44:941–9.CrossRef
7.
go back to reference Mansi R, Fleischmann A, Mäcke HR, Reubi JC. Targeting GRPR in urological cancers--from basic research to clinical application. Nat Rev Urol. 2013;10:235–44.CrossRef Mansi R, Fleischmann A, Mäcke HR, Reubi JC. Targeting GRPR in urological cancers--from basic research to clinical application. Nat Rev Urol. 2013;10:235–44.CrossRef
8.
go back to reference Kahkonen E, Jambor I, Kemppainen J, et al. In vivo imaging of prostate cancer using [68Ga]-labeled bombesin analog BAY86-7548. Clin Cancer Res. 2013;19:5434–43.CrossRef Kahkonen E, Jambor I, Kemppainen J, et al. In vivo imaging of prostate cancer using [68Ga]-labeled bombesin analog BAY86-7548. Clin Cancer Res. 2013;19:5434–43.CrossRef
9.
go back to reference Nock BA, Kaloudi A, Lymperis E, et al. Theranostic perspectives in prostate cancer with the gastrin-releasing peptide receptor antagonist NeoBOMB1: preclinical and first clinical results. J Nucl Med. 2017;58:75–80.CrossRef Nock BA, Kaloudi A, Lymperis E, et al. Theranostic perspectives in prostate cancer with the gastrin-releasing peptide receptor antagonist NeoBOMB1: preclinical and first clinical results. J Nucl Med. 2017;58:75–80.CrossRef
10.
go back to reference Zhang J, Niu G, Fan X, et al. PET using a GRPR antagonist 68 Ga-RM26 in healthy volunteers and prostate cancer patients. J Nucl Med. 2018;59:922–8.CrossRef Zhang J, Niu G, Fan X, et al. PET using a GRPR antagonist 68 Ga-RM26 in healthy volunteers and prostate cancer patients. J Nucl Med. 2018;59:922–8.CrossRef
11.
go back to reference Beer M, Montani M, Gerhardt J, et al. Profiling gastrin-releasing peptide receptor in prostate tissues: clinical implications and molecular correlates. Prostate. 2012;72:318–25.CrossRef Beer M, Montani M, Gerhardt J, et al. Profiling gastrin-releasing peptide receptor in prostate tissues: clinical implications and molecular correlates. Prostate. 2012;72:318–25.CrossRef
12.
go back to reference Körner M, Waser B, Rehmann R, Reubi JC. Early over-expression of GRP receptors in prostatic carcinogenesis. Prostate. 2014;74:217–24.CrossRef Körner M, Waser B, Rehmann R, Reubi JC. Early over-expression of GRP receptors in prostatic carcinogenesis. Prostate. 2014;74:217–24.CrossRef
13.
go back to reference D’Amico AV, Whittington R, Malkowicz SB, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998;280:969–74.CrossRef D’Amico AV, Whittington R, Malkowicz SB, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998;280:969–74.CrossRef
14.
go back to reference Reubi JC, Kvols LK, Waser B, et al. Detection of somatostatin receptors in surgical and percutaneous needle biopsy samples of carcinoids and islet cell carcinomas. Cancer Res. 1990;50:5969–77.PubMed Reubi JC, Kvols LK, Waser B, et al. Detection of somatostatin receptors in surgical and percutaneous needle biopsy samples of carcinoids and islet cell carcinomas. Cancer Res. 1990;50:5969–77.PubMed
15.
go back to reference Mansi R, Abiraj K, Wang X, et al. Evaluation of three different families of bombesin receptor radioantagonists for targeted imaging and therapy of gastrin releasing peptide receptor (GRP-R) positive tumors. J Med Chem. 2015;58:682–91.CrossRef Mansi R, Abiraj K, Wang X, et al. Evaluation of three different families of bombesin receptor radioantagonists for targeted imaging and therapy of gastrin releasing peptide receptor (GRP-R) positive tumors. J Med Chem. 2015;58:682–91.CrossRef
16.
go back to reference Gourni E, Canovas C, Goncalves V, et al. (R)-NODAGA-PSMA: a versatile precursor for radiometal labeling and nuclear imaging of PSMA-positive tumors. PLoS One. 2015;10:e0145755.CrossRef Gourni E, Canovas C, Goncalves V, et al. (R)-NODAGA-PSMA: a versatile precursor for radiometal labeling and nuclear imaging of PSMA-positive tumors. PLoS One. 2015;10:e0145755.CrossRef
17.
go back to reference Borkowski S, DOEHR O, HULTSCH C, et al. Preclinical validation of the Ga-68- bombesin antagonist BAY 86-7548 for a phase I study in prostate cancer patients. J Nucl Med. 2012;53(supplement 1):177. Borkowski S, DOEHR O, HULTSCH C, et al. Preclinical validation of the Ga-68- bombesin antagonist BAY 86-7548 for a phase I study in prostate cancer patients. J Nucl Med. 2012;53(supplement 1):177.
18.
go back to reference Benešová M, Schäfer M, Bauder-Wüst U, et al. Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J Nucl Med. 2015;56:914–20.CrossRef Benešová M, Schäfer M, Bauder-Wüst U, et al. Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J Nucl Med. 2015;56:914–20.CrossRef
19.
go back to reference Morgat C, Schollhammer R, Macgrogan G, et al. Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples. PLoS One. 2019;14:e0210905.CrossRef Morgat C, Schollhammer R, Macgrogan G, et al. Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples. PLoS One. 2019;14:e0210905.CrossRef
20.
go back to reference Spick C, Herrmann K, Czernin J. Evaluation of prostate cancer with 11C-acetate PET/CT. J Nucl Med. 2016;57:30S–7S.CrossRef Spick C, Herrmann K, Czernin J. Evaluation of prostate cancer with 11C-acetate PET/CT. J Nucl Med. 2016;57:30S–7S.CrossRef
21.
go back to reference Parent EE, Schuster DM. Update on 18F-Fluciclovine PET for prostate cancer imaging. J Nucl Med. 2018;59:733–9.CrossRef Parent EE, Schuster DM. Update on 18F-Fluciclovine PET for prostate cancer imaging. J Nucl Med. 2018;59:733–9.CrossRef
22.
go back to reference Nitsch S, Hakenberg OW, Heuschkel M, et al. Evaluation of prostate cancer with 11C- and 18F-choline PET/CT: diagnosis and initial staging. J Nucl Med. 2016;57:38S–42S.CrossRef Nitsch S, Hakenberg OW, Heuschkel M, et al. Evaluation of prostate cancer with 11C- and 18F-choline PET/CT: diagnosis and initial staging. J Nucl Med. 2016;57:38S–42S.CrossRef
23.
go back to reference Liu C, Liu T, Zhang N, et al. 68Ga-PSMA-617 PET/CT: a promising new technique for predicting risk stratification and metastatic risk of prostate cancer patients. Eur J Nucl Med Mol Imaging. 2018;45:1852–61.CrossRef Liu C, Liu T, Zhang N, et al. 68Ga-PSMA-617 PET/CT: a promising new technique for predicting risk stratification and metastatic risk of prostate cancer patients. Eur J Nucl Med Mol Imaging. 2018;45:1852–61.CrossRef
24.
go back to reference Touijer KA, Michaud L, Alvarez HAV, et al. Prospective study of the radiolabeled GRPR antagonist BAY86-7548 for positron emission tomography/computed tomography imaging of newly diagnosed prostate cancer. Eur Urol Oncol. 2018;2(2):166–73.CrossRef Touijer KA, Michaud L, Alvarez HAV, et al. Prospective study of the radiolabeled GRPR antagonist BAY86-7548 for positron emission tomography/computed tomography imaging of newly diagnosed prostate cancer. Eur Urol Oncol. 2018;2(2):166–73.CrossRef
25.
go back to reference Woythal N, Arsenic R, Kempkensteffen C, et al. Immunohistochemical validation of PSMA expression measured by 68Ga-PSMA PET/CT in primary prostate cancer. J Nucl Med. 2018;59:238–43.CrossRef Woythal N, Arsenic R, Kempkensteffen C, et al. Immunohistochemical validation of PSMA expression measured by 68Ga-PSMA PET/CT in primary prostate cancer. J Nucl Med. 2018;59:238–43.CrossRef
26.
go back to reference Moschini M, Carroll PR, Eggener SE, et al. Low-risk prostate cancer: identification, management, and outcomes. Eur Urol. 2017;72:238–49.CrossRef Moschini M, Carroll PR, Eggener SE, et al. Low-risk prostate cancer: identification, management, and outcomes. Eur Urol. 2017;72:238–49.CrossRef
27.
go back to reference Porcaro AB, Siracusano S, de Luyk N, et al. Low-risk prostate cancer and tumor upgrading in the surgical specimen: analysis of clinical factors predicting tumor upgrading in a contemporary series of patients who were evaluated according to the modified Gleason score grading system. Curr Urol. 2017;10:118–25.CrossRef Porcaro AB, Siracusano S, de Luyk N, et al. Low-risk prostate cancer and tumor upgrading in the surgical specimen: analysis of clinical factors predicting tumor upgrading in a contemporary series of patients who were evaluated according to the modified Gleason score grading system. Curr Urol. 2017;10:118–25.CrossRef
28.
go back to reference Storz E, Shah A, Zettinig O, et al. PSMA-PET/MRI-guided transrectal fusion biopsy for the detection of prostate cancer. Eur Urol Suppl. 2015;14:e217.CrossRef Storz E, Shah A, Zettinig O, et al. PSMA-PET/MRI-guided transrectal fusion biopsy for the detection of prostate cancer. Eur Urol Suppl. 2015;14:e217.CrossRef
29.
go back to reference Zettinig O, Shah A, Hennersperger C, et al. Multimodal image-guided prostate fusion biopsy based on automatic deformable registration. Int J Comput Assist Radiol Surg. 2015;10:1997–2007.CrossRef Zettinig O, Shah A, Hennersperger C, et al. Multimodal image-guided prostate fusion biopsy based on automatic deformable registration. Int J Comput Assist Radiol Surg. 2015;10:1997–2007.CrossRef
30.
go back to reference Calais J, Kishan AU, Cao M, et al. Potential impact of 68 Ga-PSMA-11 PET/CT on prostate cancer definitive radiation therapy planning. J Nucl Med. 2018;59:1714–21.CrossRef Calais J, Kishan AU, Cao M, et al. Potential impact of 68 Ga-PSMA-11 PET/CT on prostate cancer definitive radiation therapy planning. J Nucl Med. 2018;59:1714–21.CrossRef
Metadata
Title
Comparison of the radiolabeled PSMA-inhibitor 111In-PSMA-617 and the radiolabeled GRP-R antagonist 111In-RM2 in primary prostate cancer samples
Authors
Romain Schollhammer
Henri De Clermont Gallerande
Mokrane Yacoub
Marie-Laure Quintyn Ranty
Nicole Barthe
Delphine Vimont
Elif Hindié
Philippe Fernandez
Clément Morgat
Publication date
01-12-2019
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2019
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-019-0517-6

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