# Alpha-Particle Emitter Peptide Receptor Targeted Radionuclide Therapy for Neuroendocrine Tumors

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2022 · $1

## Abstract

PROJECT SUMMARY/ABSTRACT
Peptide receptor radionuclide therapy (PRRT) with [177Lu]DOTATATE improves quality of life and survival in
patients with advanced neuroendocrine tumors; however objective tumor regression is infrequent and complete
responses are exceedingly rare. On the other hand, exciting-emerging evidence suggests that PRRT with
alpha-emitters has the potential to extend PRRT to tumor regression and even complete response. In this
study we propose to develop a new theranostic pair using [203Pb]PSC-TOC (imaging) / [212Pb]PSC-TOC (alpha
emitter) for image-guided dosimetry based personalized therapy for neuroendocrine tumors. In Specific Aim 1
of the proposal, we will optimize the radiolabeling and production of [203/212Pb]PSC-TOC to prepare for its use
in clinical trials and perform a preclinical dose escalation trial in immune-competent mice to investigate drug
toxicity and the relation of toxicity with radiation dose (using residence time as a surrogate) to the organs. The
accurate measurement of radiation dose from alpha-emitters is challenging due to dependence of the dose on
the distribution of the radiopharmaceutical at cellular and subcellular level. In Specific Aim 2, we propose to
develop a surrogate for organ dosimetry based on the residence time of the radiopharmaceutical in a human
imaging trial with [203Pb]PSC-TOC, This methodology requires serial imaging over multiple days. We will then
extend the dosimetry methodology to develop a predictive model to identify the best single imaging time point
that predicts kidney accumulation, similar to our previous work with 90Y-DOTATOC, for translation of the
dosimetry procedure into the clinical practice. Finally in Specific Aim 3 we will conduct a Phase 1 dose
escalation trial of personalized dosimetry-guided therapy with [212Pb]PSC-TOC in patients with advanced stage
NETs who have progressed or are refractory to conventional PRRT with beta emitters. The dose escalation
paradigm will be based on escalating critical organ dose limits (using residence time as surrogate for
dosimetry). The primary objective of the Phase 1 clinical trial will be the identification of the maximum safe
kidney dose surrogate from treatment with [212Pb]PSC-TOC that should be used for a subsequent Phase 2
efficacy trial with the agent. As a secondary objective we will assess objective tumor response to PRRT with
[212Pb]PSC-TOC.
.

## Key facts

- **NIH application ID:** 10396517
- **Project number:** 5R01CA243014-04
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Yusuf Menda
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1
- **Award type:** 5
- **Project period:** 2019-06-03 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10396517

## Citation

> US National Institutes of Health, RePORTER application 10396517, Alpha-Particle Emitter Peptide Receptor Targeted Radionuclide Therapy for Neuroendocrine Tumors (5R01CA243014-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10396517. Licensed CC0.

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