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Introduction:
Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase Activating Peptide Receptor 1 (VPAC1) is over-expressed in prostate cancer (PC), representing a target for imaging and treatment. VPAC1 expression occurs before alterations of cell morphology or PSA elevation. We hypothesized that VPAC1 overexpressed on PC can be target tumor foci, using TP3805, a VPAC1 specific biomolecule labeled with Cu-64.
Methods:
Twenty five men undergoing radical prostatectomy were imaged preoperatively on a PET protocol targeting VPAC1. The PET images were compared to whole mount prostatectomy specimens. We performed digital autoradiography with Cu-64-TP3805 on two patients who participated in VPAC1 PET imaging, as well as 3 BPH patients, one malignant lymph node and one benign lymph node. Autoradiography was compared with prostate pathology in which tumor foci were delineated.
Results:
Prostate cancer foci (n=30/31) were identified by autoradiography. Autoradiography missed one malignant lesion due to technical artifact. Additionally 6 small cancerous lesions were identified that were not noted by histologic examinations. Seven additional lesions on autoradiography were in areas of HGPIN. The malignant and benign lymph nodes were correctly identified by autoradiography. No lesions were noted by autoradiography on the three BPH patients.
Conclusion:
VPAC1 peptide analog constructs accurately identified foci of prostate cancer on whole mount prostatectomy specimens. Several additional lesions were also identified. Detection of HGPIN is consistent with the early expression of VPAC1 prior to the modulations in cell morphology. The PPV (97%) and NPV(100%) were excellent, validating VPAC1 as a potential theranostic target for prostate cancer imaging and treatment.