Abstract
AbstractEarly and accurate detection of prostate cancer (PCa) together with effective treatment can save lives. Despite the recent advances in its treatment, the mortality trends due to PCa, in the USA, continue to be alarming with annual increase of 3%. In this brief communication, we propose a novel approach to treat PCa, its metastasis and recurrence. This is guided by a large quantity of preliminary data driven by targeting an endogenous genetic product, VPAC, expressed in high density on the cell surface at the onset of genetic mutation that ignites the cancerous transformation.A large body of preclinical and clinical data generated in our laboratory used a positron-emitting radionuclide Copper-64 (Cu-64), conjugated to a small biomolecule, TP 3805 that has a high in vivo stability and high affinity (Kd 3.1 × 10−9 M) for VPAC. The data depict high uptake of Cu-64-TP3805 in primary and metastatic lesions and malignant lymph nodes with minimal uptake in normal tissues except the liver, prompted by the hepatobiliary excretion.Reflecting on the present and planning for the future, our quest is to systematically investigate the use of the beta-emitting sister radionuclide Cu-67 to target VPAC receptors for theranostic applications of primary and metastatic PCa.
Publisher
Springer International Publishing
Reference37 articles.
1. Cancer Facts & Figures 2019. American Cancer Society. 2019. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf.
2. Baum RP, Kulkarni HR, Schuchardt C, Singh A, Wirtz M, Wiessalla S, Schottelius M, Mueller D, Klette I, Wester H-J. 177Lu-labeled prostate-specific membrane antigen radioligand therapy of metastatic castration-resistant prostate cancer: safety and efficacy. J Nucl Med. 2016;57(7):1006–13. https://doi.org/10.2967/jnumed.115.168443.
3. McBean R, O’Kane B, Parsons R, Wong D. Lu177-PSMA therapy for men with advanced prostate cancer: initial 18 months experience at a single Australian tertiary institution. J Med Imaging Radiat Oncol. 2019;63:538. https://doi.org/10.1111/1754-9485.12891.
4. Turner JH. Recent advances in theranostics and challenges for the future. Br J Radiol. 2018;91(1091):20170893. https://doi.org/10.1259/bjr.20170893; Epub 2018/03/23. PubMed PMID: 29565650; PMCID: PMC6475948.
5. Lelievre VPN, Wasche JA. In: Vaudry HAA, editor. The biological significance of PACAP and PACAP receptors in human tumors: from cell lines to cancers. Springer Publishing Co.; 2003.