# Dose-Response in Radionuclide Therapy

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $665,374

## Abstract

Dose-Response in Radionuclide Therapy
Project Summary
In this competing renewal application, our overall objective remains as previously described - to enable a patient-
specific treatment planning approach to delivering radiopharmaceutical therapy (RPT) by establishing
methodologies and developing computational tools that better predict tissue toxicity and tumor response. In the
prior grant period we addressed RPT with beta-emitters and established a methodology to plan combination
external beam radiotherapy with beta-emitter RPT. In this renewal application we propose to address the
dosimetry of alpha-particle emitters. α-particle emitters have been recognized as highly potent therapeutics that
are fundamentally novel in their mechanism and largely impervious to resistance. The recent FDA approval of
one such agent has led to numerous efforts to bring more alpha-emitter RPTs (αRPT) to the clinic. α-particles
are short-range (50 to 100 µm,) high linear energy transfer (LET) particles which cause preponderant double-
stranded break damage to DNA. Although there is a well-established dosimetry formalism for risk evaluation of
these, there is no dosimetry formalism able to account for the high LET and the short range of these to evaluate
toxicity and efficacy – therapeutic endpoints. We propose to develop a methodology that accounts for the short
range and high potency of these agents. The specific aims to do this are: 1. Measure the Relative Biological
Effectiveness (RBE) of normal tissue for α-particle emitter radiopharmaceuticals (αRPTs). No systematic
evaluation of RBE for normal tissues has been undertaken. Currently available values are largely derived from
in vitro cell studies. Since biological effect = Absorbed Dose (AD) x RBE, normal tissue RBE is needed to avoid
toxicity, plan therapy, and safely execute phase I AD escalation trials for αRPT.2. Measure tumor RBE, in vivo
for 3 tumor types, compare to RBE, in vitro. Tumor RBE is needed to assess efficacy as well as for treatment
optimization to avoid over-treating patients.3. Develop and incorporate macro to micro modeling for α-
particle emitter dosimetry into 3D-RD. The macro to micro approach developed with prior support has been
implemented for kidney dosimetry of intact antibodies, labeled with different alpha-emitters. This aim will extend
this work to peptides and small molecules and incorporate the method into the 3D-RD platform to establish a
new version of 3D-RD (α3D-RD).4. Establish models that enable combined external beam RT (XRT) with
αRPT. There is a strong rationale for combining XRT with αRPT. Such treatment has not been implemented
because a methodology that incorporates micro-scale RBE-weighted dose distribution in dose maps and dose-
volume histograms that can be used in XRT planning software does not exist. We will build upon the XRT-RPT
method that we developed previously and that is currently being used with Sm-153, (a beta-particle emitter) in
an ongoing clinical t...

## Key facts

- **NIH application ID:** 10200681
- **Project number:** 5R01CA116477-14
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Robert Francois Hobbs
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $665,374
- **Award type:** 5
- **Project period:** 2006-05-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200681

## Citation

> US National Institutes of Health, RePORTER application 10200681, Dose-Response in Radionuclide Therapy (5R01CA116477-14). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10200681. Licensed CC0.

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