# Pb-212 Peptide Receptor Targeted Prostate Cancer Therapy

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2021 · $350,330

## Abstract

The overall goal of this preclinical research program is to develop and evaluate the efficacy of targeted alpha
therapy (TAT) using an alpha emitting radiolabeled peptide antagonist which targets the bombesin receptor
(BB2r) expressed in human prostate cancer. The research program has four specific technical objectives:
  Synthesis & Validation of 212Pb-RM2: The goals of this objective are to establish and optimize methods
for synthesizing 212Pb-RM2 in high yield and purity starting with 212Pb obtained from commercially available
224Ra/212Pb radionuclide generators. Utilizing automated radiochemistry technology, routine SOP’s will be
developed for the efficient production of clinical grade 212Pb-RM2. This will also entail developing procedures
for assessing the quality control to assure that the final product meets FDA requirements for pH, sterility, and
bacterial endotoxins.
  Evaluate Efficacy of 212Pb-RM2 In Vitro: The utility of 212Pb-RM2 will be assessed across a panel of
human PC cell lines representing the spectrum of androgen dependence/independence as well as a panel of
chemotherapy resistant cell lines that are resistant to docetaxel, enzalutamide, and abiraterone. Several
chemotherapy resistant cell lines will be created during the course of this study. The effects of TAT on each cell
line will be evaluated by assessing cytotoxicity, clonogenicity, DNA damage & repair, apoptosis, cell cycle, and
protein expression of the targeted receptor, (BB2r), the androgen receptor (AR), and the most prevalent
androgen receptor splice variant in PC,(ARV7).
  Evaluate Efficacy of 212Pb-RM2 In Vivo: Initially, the in vivo stability of 212Pb-RM2 will be assessed
followed by determination of individual organ, tissue, and tumor radiation dosimetry based on 212Pb-RM2
pharmacokinetic data obtained using prostate cancer xenograft models. The maximum tolerated dose (MTD) of
212Pb-RM2 will be determined prior to performance of therapeutic efficacy evaluation. Employing a series of
CRPC xenograft models (flank, tibial, and systemic), the efficacy of 212Pb-RM2 in controlling and reducing focal
and systemic PC growth will be evaluated. Concurrent PET imaging using 68Ga-RM2 will be performed to assess
BB2r expression concurrent with BB2r targeted treatment to validate the imaging biomarker as an accurate
measure of treatment efficacy.
  Perform FDA IND Enabling Studies: Data from these studies will be used to prepare a physician
sponsored IND for submission to the FDA of the TAT agent, 212Pb-RM2. This objective will be carried out over
the course of the funding period and will include obtaining commercially prepared cGMP product, determining
internal organ radiation dosimetry, obtaining commercial single species toxicology evaluation data, development
and refinement of a standard operating procedure for the routine automated clinical preparation of 212Pb-RM2,
and performance of required preparative product scale-up runs to demonstrate that 212Pb-RM2 can be p...

## Key facts

- **NIH application ID:** 10247544
- **Project number:** 5R01CA222293-04
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** TIMOTHY J. HOFFMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $350,330
- **Award type:** 5
- **Project period:** 2018-09-12 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247544

## Citation

> US National Institutes of Health, RePORTER application 10247544, Pb-212 Peptide Receptor Targeted Prostate Cancer Therapy (5R01CA222293-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10247544. Licensed CC0.

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