An international consortium has launched a five-year initiative to improve theranostic outcomes by improving the accuracy of dosimetry, according to an editorial published April 2 in the Journal of Nuclear Medicine.
Backed by industry, government, and academic partners, the Precision Dosimetry Imaging Biomarker (PDIB) project aims to pave the way for personalized radiopharmaceutical therapy, rather than treatments being delivered as standard amounts of radioactivity at fixed intervals, noted lead author Dale Bailey, MD, of the Royal North Shore Hospital in Sydney, and colleagues.
“This approach results in most patients being underdosed, and some being overdosed, compared with what could be safely achieved through personalized treatments," the group wrote.
Despite dramatic growth in theranostics – heralded by lutetium-177 prostate-specific membrane antigen-617 (Lu-177 PSMA-617) therapy in prostate cancer and Lu-177 DOTATATE therapy in neuroendocrine tumors -- the field has largely retained a one-size-fits-all dosing model. This model was inherited from the inception of radioiodine therapy for thyroid cancer more than 80 years ago, the group explained. However, newer therapeutic radiopharmaceuticals don’t fit this dosing model, the group explained.
In the case of Lu-PSMA-617, for instance, medical physicists report that kidneys in patients receiving the therapy can receive anywhere from 4 gray (Gy) to 62 Gy, the standard unit of radiation dose, while parotid and submandibular glands can range from 13 Gy to 115 Gy. Tumor doses vary even more dramatically, spanning a 300-fold range from lowest to highest reported values across patients and lesions.
In this context, radiation dosimetry has been proposed to improve patient outcomes, yet progress has been impeded because of technical challenges, the lack of prospective clinical trial data demonstrating efficacy, and reimbursement and sustainability issues, according to the authors.
Phase 1 of the PDIB project is a three-year, $5 million effort organized into three subprojects. The first will establish an international network of four laboratories to provide accurate, traceable radioactivity measurements of key theranostic radionuclides -- including Lu-177, iodine-131, actinium-225, indium-111, lead-203, and lead-212 -- with target accuracy within ±2%.
The second subproject will harmonize SPECT/CT sensitivity calibration across the same radionuclide set, drawing on imaging sites across Europe, Australia, and North America. The third will tackle dosimetry calculation workflow variability.
“Each of these three initiatives in the first three years aims to eliminate the reproducibility and accuracy crisis that exists today in the practice of radionuclide therapy dosimetry,” the group wrote.
If these subprojects deliver as expected, a second phase is planned to run radiopharmaceutical-agnostic paired prospective clinical trials for patients with neuroendocrine tumors and of prostate cancer treatments to examine kidney, bone marrow, and tumor radiation dosimetry estimates and patient outcomes, they noted.
“International in scope and input, the PDIB project aims to both improve and standardize the use of radiation dosimetry estimates in radionuclide therapies to enable broader adoption of dosimetry-based personalized radionuclide therapies leading to better outcomes for our patients,” the group concluded.
The full editorial is available here.
