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Published in: European Journal of Nuclear Medicine and Molecular Imaging 6/2021

01-06-2021 | Prostate Cancer | Original Article

[18F]-JK-PSMA-7 and [18F]-FDG tumour PET uptake in treated xenograft human prostate cancer model in mice

Authors: Gaetan Van Simaeys, Gilles Doumont, Coraline De Maeseneire, Nicolas Passon, Simon Lacroix, Cédric Lentz, Arnaud Horion, Corentin Warnier, David Torres, Corentin Martens, Irina Vierasu, Dominique Egrise, Serge Goldman

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2021

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Abstract

Purpose

This preclinical study aims to evaluate the extent to which a change in prostate-specific membrane antigen (PSMA) expression of castration-resistant prostate cancer (CRPC) following standard treatment is reflected in [18F]JK-PSMA-7 PET/CT.

Methods

Castrated mice supplemented with testosterone implant were xenografted with human LNCaP CRPC. After appropriate tumour growth, androgen deprivation therapy (ADT) was carried out by the removal of the implant followed by a single injection of docetaxel (400 μg/20-g mouse) 2 weeks later. [18F]JK-PSMA-7 PET/CT were performed before ADT, then before and at days 12, 26, 47 and 69 after docetaxel administration. The [18F]JK-PSMA-7 PET data were compared to corresponding unspecific metabolic [18F]FDG PET/CT and ex vivo quantification of PSMA expression estimated by flow cytometry on repeated tumour biopsies.

Results

ADT alone had no early effect on LNCaP tumours that pursued their progression. Until day 12 post-docetaxel, the [18F]JK-PSMA7 uptake was significantly higher than that of [18F]FDG, indicating the persistence of PSMA expression at those time points. From day 26 onwards when the tumours were rapidly expanding, both [18F]JK-PSMA7 and [18F]FDG uptake continuously decreased although the decrease in [18F]JK-PSMA uptake was markedly faster. The fraction of PSMA-positive cells in tumour biopsies decreased similarly over time to reach a non-specific level after the same time period.

Conclusion

Applying PSMA-based imaging for therapy monitoring in patients with CRPC should be considered with caution since a reduction in [18F]JK-PSMA-7 PET uptake after successive ADT and chemotherapy may be related to downregulation of PSMA expression in dedifferentiated and rapidly proliferating tumour cells.
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Literature
4.
go back to reference Wright GL, Grob BM, Haley C, Grossman K, Newhall K, Petrylak D, et al. Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy. Urology. 1996;48:326–34.CrossRefPubMed Wright GL, Grob BM, Haley C, Grossman K, Newhall K, Petrylak D, et al. Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy. Urology. 1996;48:326–34.CrossRefPubMed
5.
go back to reference Meller B, Bremmer F, Sahlmann CO, Hijazi S, Bouter C, Trojan L, et al. Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy. EJNMMI Res. 2015;5. Meller B, Bremmer F, Sahlmann CO, Hijazi S, Bouter C, Trojan L, et al. Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy. EJNMMI Res. 2015;5.
10.
go back to reference Ettala O, Malaspina S, Tuokkola T, Luoto P, Löyttyniemi E, Boström PJ, et al. Prospective study on the effect of short-term androgen deprivation therapy on PSMA uptake evaluated with 68Ga-PSMA-11 PET/MRI in men with treatment-naïve prostate cancer. Eur J Nucl Med Mol Imaging. 2020;47:665–73. https://doi.org/10.1007/s00259-019-04635-7.CrossRefPubMed Ettala O, Malaspina S, Tuokkola T, Luoto P, Löyttyniemi E, Boström PJ, et al. Prospective study on the effect of short-term androgen deprivation therapy on PSMA uptake evaluated with 68Ga-PSMA-11 PET/MRI in men with treatment-naïve prostate cancer. Eur J Nucl Med Mol Imaging. 2020;47:665–73. https://​doi.​org/​10.​1007/​s00259-019-04635-7.CrossRefPubMed
11.
go back to reference Rosar F, Dewes S, Ries M, Schaefer A, Khreish F, Maus S, et al. New insights in the paradigm of upregulation of tumoral PSMA expression by androgen receptor blockade: enzalutamide induces PSMA upregulation in castration-resistant prostate cancer even in patients having previously progressed on enzalutamide. Eur J Nucl Med Mol Imaging. 2020;47:687–94. https://doi.org/10.1007/s00259-019-04674-0.CrossRefPubMed Rosar F, Dewes S, Ries M, Schaefer A, Khreish F, Maus S, et al. New insights in the paradigm of upregulation of tumoral PSMA expression by androgen receptor blockade: enzalutamide induces PSMA upregulation in castration-resistant prostate cancer even in patients having previously progressed on enzalutamide. Eur J Nucl Med Mol Imaging. 2020;47:687–94. https://​doi.​org/​10.​1007/​s00259-019-04674-0.CrossRefPubMed
15.
go back to reference Lückerath K, Wei L, Fendler WP, Evans-Axelsson S, Stuparu AD, Slavik R, et al. Preclinical evaluation of PSMA expression in response to androgen receptor blockade for theranostics in prostate cancer. EJNMMI Res. 2018;8:96.CrossRefPubMedPubMedCentral Lückerath K, Wei L, Fendler WP, Evans-Axelsson S, Stuparu AD, Slavik R, et al. Preclinical evaluation of PSMA expression in response to androgen receptor blockade for theranostics in prostate cancer. EJNMMI Res. 2018;8:96.CrossRefPubMedPubMedCentral
16.
go back to reference Barrett JA, Coleman RE, Goldsmith SJ, Vallabhajosula S, Petry NA, Cho S, et al. First-in-man evaluation of 2 high-affinity PSMA-avid small molecules for imaging prostate cancer. J Nucl Med. 2013;54:380–7.CrossRefPubMed Barrett JA, Coleman RE, Goldsmith SJ, Vallabhajosula S, Petry NA, Cho S, et al. First-in-man evaluation of 2 high-affinity PSMA-avid small molecules for imaging prostate cancer. J Nucl Med. 2013;54:380–7.CrossRefPubMed
17.
go back to reference Banerjee SR, Foss CA, Castanares M, Mease RC, Byun Y, Fox JJ, et al. Synthesis and evaluation of technetium-99m- and rhenium-labeled inhibitors of the prostate-specific membrane antigen (PSMA). J Med Chem. 2008;51:4504–17.CrossRefPubMedPubMedCentral Banerjee SR, Foss CA, Castanares M, Mease RC, Byun Y, Fox JJ, et al. Synthesis and evaluation of technetium-99m- and rhenium-labeled inhibitors of the prostate-specific membrane antigen (PSMA). J Med Chem. 2008;51:4504–17.CrossRefPubMedPubMedCentral
18.
go back to reference Hillier SM, Maresca KP, Lu G, Merkin RD, Marquis JC, Zimmerman CN, et al. 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen for molecular imaging of prostate cancer. J Nucl Med. 2013;54:1369–76.CrossRefPubMed Hillier SM, Maresca KP, Lu G, Merkin RD, Marquis JC, Zimmerman CN, et al. 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen for molecular imaging of prostate cancer. J Nucl Med. 2013;54:1369–76.CrossRefPubMed
19.
go back to reference Vallabhajosula S, Nikolopoulou A, Babich JW, Osborne JR, Tagawa ST, Lipai I, et al. 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen: pharmacokinetics and biodistribution studies in healthy subjects and patients with metastatic prostate cancer. J Nucl Med. 2014;55:1791–8.CrossRefPubMed Vallabhajosula S, Nikolopoulou A, Babich JW, Osborne JR, Tagawa ST, Lipai I, et al. 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen: pharmacokinetics and biodistribution studies in healthy subjects and patients with metastatic prostate cancer. J Nucl Med. 2014;55:1791–8.CrossRefPubMed
20.
go back to reference Banerjee SR, Pullambhatla M, Byun Y, Nimmagadda S, Green G, Fox JJ, et al. 68Ga-labeled inhibitors of prostate-specific membrane antigen (PSMA) for imaging prostate cancer. J Med Chem. 2010;53:5333–41.CrossRefPubMedPubMedCentral Banerjee SR, Pullambhatla M, Byun Y, Nimmagadda S, Green G, Fox JJ, et al. 68Ga-labeled inhibitors of prostate-specific membrane antigen (PSMA) for imaging prostate cancer. J Med Chem. 2010;53:5333–41.CrossRefPubMedPubMedCentral
21.
go back to reference Schäfer M, Bauder-Wüst U, Leotta K, Zoller F, Mier W, Haberkorn U, et al. A dimerized urea-based inhibitor of the prostate-specific membrane antigen for 68Ga-PET imaging of prostate cancer. EJNMMI Res. 2012;2:23.CrossRefPubMedPubMedCentral Schäfer M, Bauder-Wüst U, Leotta K, Zoller F, Mier W, Haberkorn U, et al. A dimerized urea-based inhibitor of the prostate-specific membrane antigen for 68Ga-PET imaging of prostate cancer. EJNMMI Res. 2012;2:23.CrossRefPubMedPubMedCentral
22.
go back to reference Afshar-Oromieh A, Malcher A, Eder M, Eisenhut M, Linhart HG, Hadaschik BA, et al. PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging. 2013;40:486–95.CrossRefPubMed Afshar-Oromieh A, Malcher A, Eder M, Eisenhut M, Linhart HG, Hadaschik BA, et al. PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging. 2013;40:486–95.CrossRefPubMed
23.
go back to reference Cho SY, Gage KL, Mease RC, Senthamizhchelvan S, Holt DP, Jeffrey-Kwanisai A, et al. Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a low-molecular-weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer. J Nucl Med. 2012;53:1883–91.CrossRefPubMed Cho SY, Gage KL, Mease RC, Senthamizhchelvan S, Holt DP, Jeffrey-Kwanisai A, et al. Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a low-molecular-weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer. J Nucl Med. 2012;53:1883–91.CrossRefPubMed
25.
go back to reference Hohberg M, Kobe C, Krapf P, Täger P, Hammes J, Dietlein F, et al. Biodistribution and radiation dosimetry of [18 F]-JK-PSMA-7 as a novel prostate-specific membrane antigen-specific ligand for PET/CT imaging of prostate cancer. EJNMMI Res. 2019;9:66.CrossRefPubMedPubMedCentral Hohberg M, Kobe C, Krapf P, Täger P, Hammes J, Dietlein F, et al. Biodistribution and radiation dosimetry of [18 F]-JK-PSMA-7 as a novel prostate-specific membrane antigen-specific ligand for PET/CT imaging of prostate cancer. EJNMMI Res. 2019;9:66.CrossRefPubMedPubMedCentral
26.
go back to reference Zechmann CM, Afshar-Oromieh A, Armor T, Stubbs JB, Mier W, Hadaschik B, et al. Radiation dosimetry and first therapy results with a 124 I/131 I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy. Eur J Nucl Med Mol Imaging. 2014;41:1280–92.CrossRefPubMedPubMedCentral Zechmann CM, Afshar-Oromieh A, Armor T, Stubbs JB, Mier W, Hadaschik B, et al. Radiation dosimetry and first therapy results with a 124 I/131 I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy. Eur J Nucl Med Mol Imaging. 2014;41:1280–92.CrossRefPubMedPubMedCentral
27.
go back to reference Kratochwil C, Giesel FL, Eder M, Afshar-Oromieh A, Benesová M, Mier W, et al. [177Lu] Lutetium-labelled PSMA ligand-induced remission in a patient with metastatic prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42:987.CrossRefPubMed Kratochwil C, Giesel FL, Eder M, Afshar-Oromieh A, Benesová M, Mier W, et al. [177Lu] Lutetium-labelled PSMA ligand-induced remission in a patient with metastatic prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42:987.CrossRefPubMed
36.
go back to reference Kuroda K, Liu H, Kim S, Guo M, Navarro V, Bander NH. Docetaxel down-regulates the expression of androgen receptor and prostate-specific antigen but not prostate-specific membrane antigen in prostate cancer cell lines: implications for PSA surrogacy. Prostate. 2009;69:1579–85. https://doi.org/10.1002/pros.21004.CrossRefPubMed Kuroda K, Liu H, Kim S, Guo M, Navarro V, Bander NH. Docetaxel down-regulates the expression of androgen receptor and prostate-specific antigen but not prostate-specific membrane antigen in prostate cancer cell lines: implications for PSA surrogacy. Prostate. 2009;69:1579–85. https://​doi.​org/​10.​1002/​pros.​21004.CrossRefPubMed
37.
go back to reference Liu T, Wu LY, Fulton MD, Johnson JM, Berkman CE. Prolonged androgen deprivation leads to downregulation of androgen receptor and prostate-specific membrane antigen in prostate cancer cells. Int J Oncol. 2012;41:2087–92.CrossRefPubMedPubMedCentral Liu T, Wu LY, Fulton MD, Johnson JM, Berkman CE. Prolonged androgen deprivation leads to downregulation of androgen receptor and prostate-specific membrane antigen in prostate cancer cells. Int J Oncol. 2012;41:2087–92.CrossRefPubMedPubMedCentral
39.
Metadata
Title
[18F]-JK-PSMA-7 and [18F]-FDG tumour PET uptake in treated xenograft human prostate cancer model in mice
Authors
Gaetan Van Simaeys
Gilles Doumont
Coraline De Maeseneire
Nicolas Passon
Simon Lacroix
Cédric Lentz
Arnaud Horion
Corentin Warnier
David Torres
Corentin Martens
Irina Vierasu
Dominique Egrise
Serge Goldman
Publication date
01-06-2021
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2021
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-020-05169-z

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