# Ultra-Low Count Quantitative SPECT for Alpha-Particle Therapies

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $526,222

## Abstract

PROJECT SUMMARY:
The overall goal of this project is to develop and comprehensively validate ultra-low count quantitative SPECT
(ULC-QSPECT) methods for alpha particle radiopharmaceutical therapies (αRPTs), including in a first-in-man
trial in patients with bone metastatic castration-resistant prostate cancer. αRPTs, such as those based on
Actinium-225, Thorium-227 and approved Radium-223 isotopes, are an emerging class of cytotoxic therapies
for patients with disseminated metastatic disease using internally administered alpha-particle emitting agents.
Despite the great potential of these therapies, current αRPT regimens are not personalized, with administered
activity dependent merely on mass, likely leading to non-optimal therapy. To address this challenge, there is a
crucial unmet need for methods to measure the isotope uptake, and hence the absorbed radiation dose with
these therapies, both at sites of disease and in vital dose-limiting organs. SPECT provides a clinically translatable
mechanism to achieve this goal. However, a key challenge to SPECT-based quantification is that the
administered activities in αRPTs are orders of magnitude lower than a typical SPECT scan, leading to ultra-low
detected count levels. Conventional approaches to quantification that reconstruct the isotope distribution and
estimate the regional uptake from reconstructed images are erroneous at these low count levels. To address
this issue, we put forwards a novel computational ULC-QSPECT framework for regional activity estimation from
αRPTs. These methods quantify regional uptake directly from projection data skipping the reconstruction step,
and at the same time, extract the maximal possible information from the acquired projection data. For this
purpose, we propose novel methods that accurately model the physics of imaging αRPTs, including stray-
radiation-related noise, use data from multiple-energy windows, incorporate scatter-window photons for
quantification, and process data in list-mode format. Our extensive preliminary data show that the proposed
methods result in nearly unbiased uptake and variances close to the theoretical limit. We propose to further
develop and rigorously evaluate these methods. Our proposed evaluations include studies over multiple
scanners with different detectors and different collimator configurations. Further, our goal is clinical translation
of these methods. Towards this goal, we propose to clinically evaluate these methods for measuring activity
concentrations at sites of uptake of [223Ra]RaCl2 in men with castrate resistant prostate cancer. These methods
will enable quantification of activity at disease sites in the skeleton as well as clearance through the intestine.
The approach has direct relevance to patients as it achieves noninvasive imaging of low-administered activity
therapies. Further, this proposal has substantial potential impact to improve both safety and efficacy of drug
development efforts in this rapidly evolvin...

## Key facts

- **NIH application ID:** 10446871
- **Project number:** 1R01EB031962-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Abhinav K Jha
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $526,222
- **Award type:** 1
- **Project period:** 2022-09-30 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10446871

## Citation

> US National Institutes of Health, RePORTER application 10446871, Ultra-Low Count Quantitative SPECT for Alpha-Particle Therapies (1R01EB031962-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10446871. Licensed CC0.

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