Are you ready for targeted RPT?



Radiation oncology is about to change. If the last 20 years heralded a technological revolution in external beam delivery, the next 10 years will see the incorporation of targeted radiopharmaceutical therapy (RPT) into everyday practice. It’s already happening. In July 2022, ASTRO published their RPT framework for trainees and prioritized RPT as “a leading area for new therapeutic development”.  Just this past year, the first targeted RPT agent for prostate cancer, Pluvicto (Lu-177), gained FDA approval, and hundreds of clinics throughout the United States have started using it.

Cellular radiation targeting emerged from our deep understanding of biochemistry and the specific biomarkers present on the surface of cancer cells. New RPT agents target cell surface biomarkers by using molecules designed to carry a lethal radioactive payload directly to individual cells. In theory, if the targeting is specific to just cancer cells, we can selectively deliver therapeutic radiation doses on a cellular level with the hope of leaving adjacent normal cells relatively unscathed. Pluvicto uses this strategy. It targets prostate specific membrane antigen (PSMA) and delivers a radioactive payload to castrate resistant metastatic prostate cancer, and patients are seeing an overall survival benefit from this approach.

Where does medical physics fit in? Targeted RPT is currently managed by nuclear medicine in most community practice settings, but it doesn’t take much of a mental leap to realize that every medical physics discipline is involved with, perhaps, therapeutic medical physics lagging the farthest behind (mostly from lack of proximity to the actual procedure). Soon, a successful course of RPT will involve a careful, multidisciplinary approach.

A physicist servicing as a radiation safety officer (RSO) will need to setup a new program for RPT and maintain regulatory requirements and/or NRC regulations.  The RSO needs to perform dose calibrator QA and calibration create infusion protocols, patient release criteria and instructions, decay storage instructions, and policies for radiation contamination control.

An Imaging physicist needs to oversee SPECT/CT & PET/CT quantification, calibration, QA, and prepare the Nuclear Medicine Department for a new way of thinking with patient imaging over multiple time points.

The therapy physicist needs to consider prospective treatment planning which includes time integrated activity curve fitting and multiple timepoint image registration that ultimately results in an isodose plan to use not only for the patient’s RPT but will become increasingly necessary for retreatment with external beam.

Targeted RPT is in its infancy, but the future applications seem to be limitless. Many late-stage clinical trials are finishing for indications beyond metastatic prostate cancer. Pharmaceutical companies are operating under the assumption that within 10 years, 50% of solid tumors will be candidates for targeted RPT, likely as part of combined modality therapy. Many therapeutic medical physicists will encounter targeted RPT for the first time when a physician walks into their office and presents a patient who needs their external beam dose summed with their recent targeted RPT dose. Are you ready?