Abstract 1485: Pilot study of VPAC1 targeted PET imaging of prostate cancer
Authors: Trabulsi Edouard J. , Kumar Pradeep , Tripathi Sushil , Birbe Ruth , McCue Peter , Wickstrom Eric , Intenzo Charles , Kim Sung , Den Robert , Gomella Leonard , Thakur Mathew L. 
Published: August 2015

Introduction: Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase Activating Peptide Receptor 1 (VPAC1) is over-expressed in prostate cancer (PC), representing a highly suitable target for imaging and treatment. VPAC1 expression occurs at the onset of the malignancy, before alterations of cell morphology, which may be prior to elevation of serum PSA. We have successfully used VPAC1 receptor-specific peptide constructs to image breast cancer in experimental animal models, and in humans. We hypothesized that VPAC1 expressed in high density on PC can be targeted for detection of intraprostatic tumor foci, as correlated with whole mount radical prostatectomy specimens, using TP3805, a VPAC1 specific biomolecule labeled with Cu-64 a PET imaging radionuclide.

Methods: Twenty five men with prostate cancer undergoing radical prostatectomy were imaged preoperatively as part of a PET imaging protocol targeting VPAC1. The PET images were compared to whole mount radical prostatectomy pathologic analysis. De-paraffinized whole mount pathology slides from two patients who participated in VPAC1 PET imaging protocol, as well as slides from 3 BPH patients, one malignant lymph node and one benign lymph node were incubated with Cu-64-TP3805, washed thoroughly with PBS, dried and subjected to 15 second digital autoradiography. Slides were then H&E stained and autoradiography images were compared with prostate H&E staining in which tumor foci were delineated.

Results: Prostate cancer foci (n = 30/31) were identified by autoradiography imaging. Autoradiography missed one malignant lesion due to technical artifact. Additionally 6 small cancerous lesions were identified by autoradiography that were not previously noted by histologic examinations. A total of 7 additional lesions seen by autoradiography in areas without prostate cancer foci corresponded to areas of high grade prostatic intraepithelial neoplasia (HGPIN). The positive lymph node and the benign lymph node were correctly identified by autoradiography. For the three BPH patients without any cancer, no lesions were noted by autoradiography.

Conclusion: VPAC1 peptide analog constructs accurately identified foci of prostate cancer on whole mount radical 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.

Support: NIH R01 CA157372-01 and by NuView, Inc. (MLT).

Citation Format: Edouard J. Trabulsi, Pradeep Kumar, Sushil Tripathi, Ruth Birbe, Peter McCue, Eric Wickstrom, Charles Intenzo, Sung Kim, Robert Den, Leonard Gomella, Mathew L. Thakur. Pilot study of VPAC1 targeted PET imaging of prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1485. doi:10.1158/1538-7445.AM2015-1485