Cloud/Subscription based, Customer-Responsive Dosimetry Tool for alpha-Particle Emitters

Direct to Phase 2 SBIR Cloud/Subscription based, Customer-Responsive Dosimetry Tool for α-Particle Emitters PROJECT SUMMARY Radiopharmaceutical therapy (RPT) – defined as a form of cancer therapy that uses targeted radionuclides to deliver radiation to cancer cells and their microenvironment – is a growing area with many pharmaceutical companies developing products in this area. The dosimetric evaluation of therapeutic radiopharmaceuticals is a key requirement for regulatory approval and treatment planning. Currently available dosimetry software packages were developed for diagnostic imaging or therapies involving beta emitters applications. These do not include features essential for α-emitter radiopharmaceutical therapy (αRPT). In this Phase II application, we will build upon our previous work to transition from a radiological protection-based dosimetry paradigm, where the biologic endpoint is long-term stochastic effects, to one whose endpoint is normal tissue toxicity and therapeutic efficacy. We will implement a methodology that uses macroscopic activity measurements to derive activity distributions at the microscopic level (we call it macro-to-micro or M2µ). Because of the short range and high potency of α-particles, and the inability to assess microscale activity distributions directly in human patients with current imaging technology, the M2µ formalism is essential to assessing normal organ toxicity for αRPT. The M2µ methodology was developed at Johns Hopkins and licensed to Rapid®, LLC. No other dosimetry product has implemented the M2µ technology. The work proposed in this Phase II application will be incorporated into 3D-RD-S, our cloud-based Medical Internal Radiation Dose (MIRD) Committee S-value-compatible dose calculation tool. Based on clients’ requests, this area has been identified as the area of greatest need. The specific aims for this application are: 1. Establish a library of microscale S-values for three dose-limiting tissues relevant to αRPT (kidneys, bone marrow, salivary glands). 2. Establish corresponding apportionment factors that map whole-organ activity concentration to sub-structure activity concentrations 3. Implement customizable M2µ dosimetry by allowing user uploads of a microscale geometry for a given macroscopically defined tissue. 4. Integrate, and computationally test, the M2µ functionality within the 3D-RD-S platform; using the already built-in uncertainty calculation platform, calculate the uncertainty associated with microscale absorbed doses. 5. Since α-emitter dosimetry and the M2µ method are likely to be unfamiliar to users that are new to αRPT, we will develop on-line educational materials accessible within the 3D-RD-S platform. Aim 5 reflects the importance of educating both αRPT practitioners and the regulatory authorities regarding the special considerations related to α-emitter dosimetry. The on-line material builds on the 3D-RD-S cloud-based platform. Support for this grant will complete a component of a multi-component subscription-based and browser-accessible dosimetry platform for αRPT that will eventually include all of the essential elements needed to support treatment planning of cancer patients undergoing α-emitter radiopharmaceutical therapy.