VPAC1-targeted PET/CT scan: improved molecular imaging for the diagnosis of prostate cancer using a novel cell surface antigen
Current approaches to prostate cancer screening and diagnosis are plagued with limitations in diagnostic accuracy. There is a compelling need for biomolecular imaging that will not only detect prostate cancer early but also distinguish prostate cancer from benign lesions accurately. In this topic paper, we review evidence that supports further investigation of VPAC1-targeted PET/CT imaging in the primary diagnosis of prostate cancer.
A non-systematic review of Medline/PubMed was performed. English language guidelines on prostate cancer diagnosis and management, original articles, and review articles were selected based on their clinical relevance.
VPAC1 receptors were overexpressed 1000 times more in prostate cancer than benign prostatic stromal tissue. In vitro and in vivo studies showed that Copper-64 labeled analogs of VPAC1 ligands can be synthesized with high radiochemical efficiency and purity. The radioactive probes had excellent VPAC1 receptor binding specificity and affinity. They had good biochemical stability in vitro and in mouse and human serum. They had minimal urinary excretion, which made them favorable for prostate cancer imaging. Initial feasibility study in men with prostate cancer showed that the probes were safe with no reported adverse reaction. 64Cu-TP3805 PET/CT detected 98% of prostate cancer lesions and nodal metastasis as confirmed with whole mount histopathological evaluation.
VPAC1 receptors are promising targets for biomolecular imaging of primary prostate cancer that can distinguish malignant from benign lesions non-invasively. Further investigations are warranted to validate initial findings and define the clinical utilities of VPAC1-targeted PET imaging for prostate cancer diagnosis and management.
KeywordsProstate cancer Positron-emission tomography VPAC1 receptors Copper-64 Biomolecular imaging
Dalton, atomic mass unit
Digital rectal exam
Exploratory Investigational New Drug
Hematoxylin and eosin
Magnetic resonance imaging
Prostate Imaging Reporting and Data System
Positive predictive value
Prostate specific antigen
Standard uptake value
Transgenic adenocarcinoma of the mouse prostate
Vasoactive intestinal peptide
Pituitary adenylate cyclase activating peptide
HT: data analysis and manuscript writing. LGG: project development and manuscript editing. MLT: project development, data collection, data analysis, and manuscript editing. EJT: project development, data collection, data analysis, and manuscript editing.
Compliance with ethical standards
Conflict of interest
MLT is a consultant to NuView Life Sciences. HT, LGG, and EJT declare no relevant financial interests.
Research involving human participants
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 7.Bryant RJ, Sjoberg DD, Vickers AJ, Robinson MC, Kumar R, Marsden L et al (2015) Predicting high-grade cancer at ten-core prostate biopsy using four kallikrein markers measured in blood in the ProtecT study. J Natl Cancer Inst 107(7):djv095. https://doi.org/10.1093/jnci/djv095 CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Sanda MG, Cadeddu JA, Kirkby E, Chen RC, Crispino T, Fontanarosa J, Freedland SJ, Greene K, Klotz LH, Makarov DV, Nelson JB, Rodrigues G, Sandler HM, Taplin ME, Treadwell JR (2017) Clinically Localized Prostate Cancer: AUA/ASTRO/SUO Guideline. Part I: Risk Stratification, Shared Decision Making, and Care Options. J Urol. https://doi.org/10.1016/j.juro.2017.11.095 Google Scholar
- 11.National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Prostate cancer. (Version 2.2017). Prostate cancer. Version 02.2017Google Scholar
- 12.Muller BG, Shih JH, Sankineni S, Marko J, Rais-Bahrami S, George AK et al (2015) Prostate cancer: interobserver agreement and accuracy with the revised prostate imaging reporting and data system at multiparametric mr imaging. Radiol Radiol Soc N Am 277(3):741–750Google Scholar
- 23.Zhang K, Aruva MR, Shanthly N, Cardi CA, Patel CA, Rattan S et al (2007) Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) receptor specific peptide analogues for PET imaging of breast cancer: in vitro/in vivo evaluation. Regul Pept 144(1–3):91–100CrossRefPubMedPubMedCentralGoogle Scholar