Cloud/web-based platform for quantitative spect reconstruction of therapeutic radionuclides

The National Cancer Institute (NCI) awarded a $1,003,173 Project Grant under the Cancer Treatment Research program (CFDA 93.395) to Radiopharmaceutical Imaging And Dosimetry, LLC, a company based in Baltimore, Maryland. The funding supports the development of a prototype web/cloud-based quantitative SPECT reconstruction software system for use in clinical trials and ultimately clinical dosimetry for radiopharmaceutical therapy (RPT). The software aims to enable accurate quantitative imaging and personalized dosimetry for emerging RPT approaches, particularly those utilizing alpha-emitting radionuclides. The project will run from February 1, 2025 to January 31, 2027. Radiopharmaceutical Imaging And Dosimetry, LLC has also received multiple sub-grant awards from Johns Hopkins University to collaborate on related projects advancing precision medicine techniques in cancer treatment through innovative software and computational solutions.

Abstract

Radiopharmaceutical therapy (RPT) is an emerging cancer treatment that delivers radiation directly to cancer cells. The commercial success of 223RA (xofigotm) for resistant metastatic prostate cancer, lutathera for neuroendocrine tumors, and approval of pluvicto for prostate cancer provides an example of the therapeutic and commercial potential of this modality. In addition, drug companies have large libraries of targets and targeting molecules. Progress in chelators and commercial availability of alpha emitters such as 212PB, 227TH, and 225AC and the large number of clinical trials of rpts and companies involved in RPT development are indicators that RPT is poised to become an important tool for cancer therapy. Multiple companies and academic centers are developing drugs based on alpha emitters. For example, bayer has presented data on TH-227-based agents targeting CD22, HER2, psma and FGFR2 receptors, and rayzebio on AC-225-dotate. FDA approval of RPT agents requires tumor and normal tissue dose estimates. European regulations mandate personalized dosimetry. Optimal use of rpts requires a precision medicine approach based on quantitative imaging and dosimetry. The foundation of reliable dosimetry is quantitative imaging. Commercial quantitative spect/CT software packages are not aimed at therapeutic radionuclides and especially not alpha emitters: their reconstruction methods are too simple to support accurate quantitative reconstructions of these radionuclides. Quantitative spect of two simultaneously present radionuclides is not available and would be provided in this work. The overall goal of this project is to develop a prototype web/cloud-based quantitative spect reconstruction software system that can be used for clinical trials and ultimately for clinical RPT dosimetry. The ability to directly image RA-223, TH-227/RA-223, PB-212, and AC-225 (via FR-221)/BI-213 has the potential to expedite trials by eliminating the time and expense needed to develop surrogates, to help better select patients likely to respond, and to tailor doses to maximize efficacy while reducing toxicity. To develop this system, we propose to (1) improve existing quantitate methods by improving scatter and downscatter modeling and adding rigorous partial volume compensation; (2) perform experiments needed to select appropriate energy windows and collimators for quantitative imaging of these radionuclides (3) develop practical calibration methods that can be translated to clinical sites (4) validate and characterize the methods developed above so they can be applied appropriately and there is an understanding of their limits and uncertainties; and (5) in parallel, integrate quantitative spect into rapid's web/cloud-based dosimetry platform. Successful completion of this would provide a platform for quantitative spect of radionuclides used in alpha emitter therapy that are well characterized and validated and could be immediately used in clinical trials and serve as the basis for a product designed for clinical dosimetry.