Monitoring PSMA Responses to ADT in Prostate Cancer Patient-Derived Xenograft Mouse Models Using [ 18 F]DCFPyL PET Imaging.

Autor: Roy J; Molecular Imaging Program, NCI/NIH, Center for Cancer Research, National Cancer Institute, Building 10, Room B3B406, Bethesda, MD, 20892, USA., White ME; Laboratory of Genitourinary Cancer Pathogenesis NCI/NIH, Bethesda, MD, USA., Basuli F; Chemistry and Synthesis Center, NHLBI/NIH, Rockville, MD, USA., Opina ACL; Chemistry and Synthesis Center, NHLBI/NIH, Rockville, MD, USA., Wong K; Molecular Imaging Program, NCI/NIH, Center for Cancer Research, National Cancer Institute, Building 10, Room B3B406, Bethesda, MD, 20892, USA., Riba M; Laboratory of Genitourinary Cancer Pathogenesis NCI/NIH, Bethesda, MD, USA., Ton AT; Molecular Imaging Program, NCI/NIH, Center for Cancer Research, National Cancer Institute, Building 10, Room B3B406, Bethesda, MD, 20892, USA., Zhang X; Chemistry and Synthesis Center, NHLBI/NIH, Rockville, MD, USA., Jansson KH; Laboratory of Genitourinary Cancer Pathogenesis NCI/NIH, Bethesda, MD, USA., Edmondson E; Pathology/Histotechnology Laboratory, Leidos, Inc./Frederick National Laboratory for Cancer Research, NCI, Frederick, MD, USA., Butcher D; Pathology/Histotechnology Laboratory, Leidos, Inc./Frederick National Laboratory for Cancer Research, NCI, Frederick, MD, USA., Lin FI; Molecular Imaging Program, NCI/NIH, Center for Cancer Research, National Cancer Institute, Building 10, Room B3B406, Bethesda, MD, 20892, USA., Choyke PL; Molecular Imaging Program, NCI/NIH, Center for Cancer Research, National Cancer Institute, Building 10, Room B3B406, Bethesda, MD, 20892, USA., Kelly K; Laboratory of Genitourinary Cancer Pathogenesis NCI/NIH, Bethesda, MD, USA., Jagoda EM; Molecular Imaging Program, NCI/NIH, Center for Cancer Research, National Cancer Institute, Building 10, Room B3B406, Bethesda, MD, 20892, USA. ejagoda@mail.nih.gov.
Jazyk: angličtina
Zdroj: Molecular imaging and biology [Mol Imaging Biol] 2021 Oct; Vol. 23 (5), pp. 745-755. Date of Electronic Publication: 2021 Apr 23.
DOI: 10.1007/s11307-021-01605-0
Abstrakt: Purpose: PSMA overexpression has been associated with aggressive prostate cancer (PCa). However, PSMA PET imaging has revealed highly variable changes in PSMA expression in response to ADT treatment ranging from increases to moderate decreases. To better understand these PSMA responses and potential relationship to progressive PCa, the PET imaging agent, [ 18 F]DCFPyL, was used to assess changes in PSMA expression in response to ADT using genomically characterized LuCaP patient-derived xenograft mouse models (LuCaP-PDXs) which were found to be sensitive to ADT (LuCaP73 and LuCaP136;CS) or resistant (LuCaP167;CR).
Methods: [ 18 F]DCFPyL (2-(3-{1-carboxy-5-[(6-[ 18 F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) was used to assess PSMA in vitro (saturation assays) in LuCaP tumor membrane homogenates and in vivo (imaging/biodistribution) in LuCaP-PDXs. Control and ADT-treated LuCaPs were imaged before ADT (0 days) and 2-, 7-, 14-, and 21-days post-ADT from which tumor:muscle ratios (T:Ms) were determined and concurrently tumor volumes were measured (caliper). After the 21-day imaging, biodistributions and histologic/genomic (PSMA, AR) analysis were done.
Results: [ 18 F]DCFPyL exhibited high affinity for PSMA and distinguished different levels of PSMA in LuCaP tumors. Post-ADT CS LuCaP73 and LuCaP136 tumor volumes significantly decreased at day 7 or 14 respectively vs controls, whereas the CR LuCaP167 tumor volumes were minimally changed. [ 18 F]DCFPyL imaging T:Ms were increased 3-5-fold in treated LuCaP73 tumors vs controls, while treated LuCaP136 T:Ms remained unchanged which was confirmed by day 21 biodistribution results. For treated LuCaP167, T:Ms were decreased (~ 45 %) vs controls but due to low T:M values (<2) may not be indicative of PSMA level changes. LuCaP73 tumor PSMA histologic/genomic results were comparable to imaging/biodistribution results, whereas the results for other tumor types varied.
Conclusion: Tumor responses to ADT varied from sensitive to resistant among these LuCaP PDXs, while only the high PSMA expressing LuCaP model exhibited an increase in PSMA levels in response to ADT. These models may be useful in understanding the clinical relevance of PSMA PET responses to ADT and potentially the relationship to disease progression as it may relate to the genomic signature.
(© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)
Databáze: MEDLINE
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