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

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...

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Bibliographic Details
Published in:Molecular imaging and biology 2021-10, Vol.23 (5), p.745-755
Main Authors: Roy, Jyoti, White, Margaret E., Basuli, Falguni, Opina, Ana Christina L., Wong, Karen, Riba, Morgan, Ton, Anita T., Zhang, Xiang, Jansson, Keith H., Edmondson, Elijah, Butcher, Donna, Lin, Frank I., Choyke, Peter L., Kelly, Kathleen, Jagoda, Elaine M.
Format: Article
Language:English
Subjects:
Androgen Antagonists - therapeutic use
Animal models
Animals
Antineoplastic Agents, Hormonal - therapeutic use
Biodistribution
Carbonyl compounds
Carbonyls
Cell Line, Tumor
Disease Models, Animal
Fluorine isotopes
Gene expression
Genomics
Humans
Imaging
Lysine - administration & dosage
Lysine - analogs & derivatives
Lysine - metabolism
Lysine - pharmacokinetics
Male
Medical imaging
Medicine
Medicine & Public Health
Mice
Muscles
Patients
Positron emission
Positron emission tomography
Positron-Emission Tomography - methods
Prostate cancer
Prostate-Specific Antigen - analysis
Prostate-Specific Antigen - chemistry
Prostate-Specific Antigen - metabolism
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - metabolism
Pyridines
Radiology
Research Article
Tomography
Tumors
Urea - administration & dosage
Urea - analogs & derivatives
Urea - metabolism
Urea - pharmacokinetics
Xenograft Model Antitumor Assays
Xenografts
Xenotransplantation
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Summary: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 (
ISSN:1536-1632
1860-2002
DOI:10.1007/s11307-021-01605-0