Advancing Prostate Cancer Theranostics with Novel ImmunoPET Agents

Prostate cancer is a pressing global health concern, and the search for effective theranostic solutions remains at the forefront of our mission. Currently, prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals stand as the primary and clinically available theranostic agent for prostate cancer. However, we are faced with a significant challenge as a substantial number of metastatic castration-resistant prostate cancer (mCRPC) patients are PSMA-negative at the time of diagnosis or may become PSMA-negative as their treatment progresses.

Our team, focused on the field of prostate cancer theranostics, is currently working on an innovative strategy targeting CD46, a biomarker found on prostate cancer cells, providing a promising solution to current limited PSMA-based approaches. We have developed Zirconium-89 labeled antibody, [89Zr]-DFO-YS5, for immunoPET imaging of prostate cancer tumors that specifically detects PSMA positive and PSMA null tumors in localized, metastatic, adenocarcinoma, NEPC tumor models. This immunoPET agent is currently undergoing clinical testing in mCRPC patients (NCT05245006). CD46 targeted therapeutic molecules [225Ac]-DOTA-YS5 and [225Ac]Macropa-PEG4-YS5 were also developed after radiolabeling with Actinium-225, an alpha particle-emitting radioisotope. This novel therapeutic molecule delivers a substantially high therapeutic radiation dose to the tumors, while sparing healthy tissues from unnecessary radiation exposure.

research diagram

Figure: Development of the PET imaging probe [89Zr]-DFO-YS5 and alpha particle therapy agents [225Ac]-DOTA-YS5 and [225Ac]Macropa-PEG4-YS5 for prostate cancer theranostics.  

For more information, refer to our published work:

  1. Bidkar AP, Wang S, Bobba KN, Chan E, Bidlingmaier S, Egusa EA, Peter R, Ali U, Meher N, Wadhwa A, Dhrona S, Dasari C, Beckford-Vera D, Su Y, Tang R, Zhang L, He J, Wilson DM, Aggarwal R, VanBrocklin HF, Seo Y, Chou J, Liu B, Flavell RR. Treatment of Prostate Cancer with CD46-targeted 225Ac Alpha Particle Radioimmunotherapy. Clin Cancer Res. 2023 May 15;29(10):1916-1928. doi: 10.1158/1078-0432.CCR-22-3291. PMID: 36917693; PMCID: PMC10183825.
  2. Bobba KN, Bidkar AP, Wadhwa A, Meher N, Drona S, Sorlin AM, Bidlingmaier S, Zhang L, Wilson DM, Chan E, Greenland NY, Aggarwal R, VanBrocklin HF, He J, Chou J, Seo Y, Liu B, Flavell RR. Development of CD46 targeted alpha theranostics in prostate cancer using 134Ce/225Ac-Macropa-PEG4-YS5. Theranostics. 2024 Jan 27;14(4):1344-1360. doi: 10.7150/thno.92742. PMID: 38389832; PMCID: PMC10879874.
  3. Wang S, Li J, Hua J, Su Y, Beckford-Vera DR, Zhao W, Jayaraman M, Huynh TL, Zhao N, Wang YH, Huang Y, Qin F, Shen S, Gioeli D, Dreicer R, Sriram R, Egusa EA, Chou J, Feng FY, Aggarwal R, Evans MJ, Seo Y, Liu B, Flavell RR, He J. Molecular Imaging of Prostate Cancer Targeting CD46 Using ImmunoPET. Clin Cancer Res. 2021 Mar 1;27(5):1305-1315. doi: 10.1158/1078-0432.CCR-20-3310. Epub 2020 Dec 8. PMID: 33293372; PMCID: PMC7925362.

Our work has been highlighted with an image from our recent study as the cover for the Clinical Cancer Research Journal (Vol 29 No 10) and in UroToday (visit the link for more information).