Increased PSMA Expression in Castration-Resistant Prostate Cancer Metastases 3 Months After Initiation of Enzalutamide Indicated by 18F-DCFPyL PET/CT

Abstract

Radioisotope-labeled prostate-specific membrane antigen PET/CT is increasingly used for detection of prostate cancer most often in the setting of biochemical recurrence or in primary staging. This report shows increased PSMA expression in lymph node metastases 3 months after initiation of enzalutamide for castration-resistant prostate cancer, whereas lymph node volume and serum prostate-specific antigen decreases over time. This case demonstrates that increasing 18F-DCFPyL uptake after initiation of androgen deprivation therapy should not be confused with disease progression.

Prognostic and Theranostic Applications of Positron Emission Tomography for a Personalized Approach to Metastatic Castration-Resistant Prostate Cancer

“…Holland et al [27] Pre-clinical 89 Zr-DFO-J591 PSMA Immuno-PET with 89 Zr-DFO-J591 resulted capable of detecting PSMA-expressing tumor xenograft in mice.…”

“…PSMA inhibitors (PSMAi) expolit glutamate carboxypeptidase enzymatic activity of the extracellular domain of PSMA and can be labeled either with positron-emitting nuclides (e.g., 68 Ga, 64 Cu, 18 F) for imaging or with beta/alpha emitting radioisotopes (e.g., 177 Lu, 213 Bi, 225 Ac) for radionuclide therapy. Monoclonal antibodies (MoAbs) have also been developed: 111 In-capromab is directed towards the intracellular PSMA domain and is utilized for scintigraphic imaging, 89 Zr-DFO-J591 targets the extracellular portion of PSMA and is suitable for PET imaging (figure created with Biorender.com (accessed on 8 March 2021)).…”

“…J591 MoAb was firstly conjugated with the gamma-emitting 111 In and, subsequently, with the positron-emitter zirconium-89 ( 89 Zr). Holland et al reported first pre-clinical data on using the MoAb J591, conjugated with 89 Zr through the chelator desferrioxamine (DFO) [27]. The radiocompound, namely 89 Zr-DFO-J591, was tested first in vitro and then in 2 groups of nude mice bearing sub-cutaneous LNCaP (PSMA positive) or PC-3 (PSMA negative) tumor xenografts.…”

“…Holland et al reported first pre-clinical data on using the MoAb J591, conjugated with 89 Zr through the chelator desferrioxamine (DFO) [27]. The radiocompound, namely 89 Zr-DFO-J591, was tested first in vitro and then in 2 groups of nude mice bearing sub-cutaneous LNCaP (PSMA positive) or PC-3 (PSMA negative) tumor xenografts. The authors found that 89 Zr-DFO-J591 bound to PSMA-expressing tumor cells with an immunoreactive fraction of 0.95 ± 0.03.…”

“…The radiocompound, namely 89 Zr-DFO-J591, was tested first in vitro and then in 2 groups of nude mice bearing sub-cutaneous LNCaP (PSMA positive) or PC-3 (PSMA negative) tumor xenografts. The authors found that 89 Zr-DFO-J591 bound to PSMA-expressing tumor cells with an immunoreactive fraction of 0.95 ± 0.03. Furthermore, micro-PET examination showed that 89 Zr-DFO-J591 was capable to detect PSMA-positive xenografts (i.e., LNCaP) with tumor-to-background > 20 between 48-144 h post-injection.…”