# Core 1: Animal Models, Pathology and Tissue

> **NIH NIH P01** · JOHNS HOPKINS UNIVERSITY · 2024 · $216,032

## Abstract

Project Summary
Alpha-particle -emitter radiopharmaceutical therapy (αRPT) is a new and rapidly evolving therapeutic modality
that can deliver highly potent, alpha-particles to disseminated cancer metastases, with 100 micron precise
radiation trajectory, and less toxicity in patients. Since almost all of the radionuclides used in αRPT emit photons
that can be imaged non-invasively, valuable pharmacokinetic and anatomical data is provided. Precisely
targeting the cancer without side effects to normal tissues would be a breakthrough for patient care. All patients
are different though and each patient may need αRPT dose adjustments but current implemented αRPT
protocols don’t achieve this goal. To address this unmet need, in experiments outlined in the application,
facilitated by Core B, dosimetry-driven treatment planning, in combination with a radiobiologic understanding of
how absorbed dose translates to biologic effect, will reduce the scope of human experimentation (costs and
timeline) needed to clinically optimize αRPT. To achieve these goals and test project hypotheses, Projects 1-4
address multiple steps to improve αRPT and rely on the Animal Models, Pathology and Tissue Core to facilitate
all projects using animal models or human tissue-based analyses. Core B molecular tissue techniques will
address the role of DNA damage by αRPT and DNA repair pathway inhibitors in project 4. The overall hypothesis
of this PPG is that αRPT is a systemic cancer therapy modality that is particularly applicable to targeting
metastatic cancer; and far less susceptible to conventional resistance mechanisms; yet it is amenable to
dosimetry-driven treatment planning. In the experiments proposed, S values measurements can be perfected
down to a microscale to focus the alpha-particle delivered dose on cancer and eliminate peripheral collateral
organ damage. The Animal models, Pathology and Tissue Core are led by an experienced veterinary
pathologist/toxicologist and a MD pathologist at Johns Hopkins University who have long contributed to cancer
therapeutic research at this institution. The emphasis of the Core is to assist PIs of the four projects in three
different areas, (1) animal models (2) necropsy, tissue sampling, processing, and histopathology with αRPT
image correlation and (3) in situ assays on human and animal tissues to assess DNA damage and repair.
Standard operating procedures of the Core for biospecimens incorporate the guidelines as outlined by the 2011
Revised NCI Best Practices for Biospecimen Resources. Rigor and reproducibility, as well as sex as a biological
variable and appropriate animal numbers will be addressed in experimental design. The PIs of this Core have
the necessary expertise and methodologies to provide pathology consultation for use of the human specimens
and animal tissues for the proposed studies with a combined 30 years of collaboration with members of this
program project and JHU research community. This valued knowledge and ...

## Key facts

- **NIH application ID:** 10931461
- **Project number:** 5P01CA272222-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** KATHLEEN Louise GABRIELSON
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $216,032
- **Award type:** 5
- **Project period:** 2023-09-19 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10931461

## Citation

> US National Institutes of Health, RePORTER application 10931461, Core 1: Animal Models, Pathology and Tissue (5P01CA272222-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10931461. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*