Friday, November 3, 2023

High-dose precision radionuclide therapy (PRnT) by direct interstitial injection: optimizing therapeutic ratios for safe and effective delivery of high-dose radionuclide therapy in treating solid tumors

On November 3, 2023, the Georgian Health Physics Association welcomed Darrell Fisher, a seasoned nuclear medicine physicist representing Versant Medical Physics & Radiation Safety, to share his groundbreaking work in precision radionuclide therapy.   Fisher received his Ph.D. in nuclear engineering sciences from the University of Florida and carried a rich legacy of a 35-year tenure as a senior scientist and the lead of the Isotope Sciences Program at Pacific Northwest National Laboratory. His career also showcases his role as a science advisor to the U.S. Customs and Border Protection Commissioner between 2003 and 2005. Notably, Dr. Fisher has been a pivotal figure in leadership of the Health Physics Society, serving on its board of directors, as treasurer, and later as president of the society.

Dr. Darrell Fisher presents to GHPA members

Fisher's presentation was centered around overcoming the challenges in radiation therapy, primarily the adverse effects on non-target organs and tissues due to unwanted radiation doses. He introduced an ideal radionuclide therapy model that enables nearly 100% treatment dose delivery within the clinical target volume, by localizing the dose and minimizing radionuclide out-migration from tumors. The breakthrough approach of direct intra-tumoral injection of yttrium-90 microparticles delivered in a sterile polymer composite matrix, as shared by Dr. Fisher, paves the way for potential oncology applications in both human and veterinary patients, especially for tumors that are poor candidates for surgical excision or external beam therapy.

Following the presentation, several questions from the audience were posed, leading to a lively discussion on the topic. High interest shown by the audience reflected the potential this research holds for the future of radiation therapy. The video recording of Dr. Fisher's presentation and the abstract are available below.


Darrell R. Fisher, Ph.D
Versant Medical Physics & Radiation Safety
University of Washington, Seattle 

Michael K. Korenko 
Vivos, Inc.

The limiting constraint in all modes of radiation therapy is unwanted dose to non-target normal organs and tissues, which can cause severe side-effects. An ideal radionuclide therapy places 100% of the treatment dose uniformly within the clinical target volume without radionuclide out-migration from the tumor. Such treatment can be achieved by employing an optimum radionuclide and chemical form with carrier properties that facilitate injection, placement, and in-tumor retention. An optimized radiation dose achieves effective tumor destruction while preventing or minimizing normal tissue adverse reactions. Yttrium-90 emits no gamma rays and can be handled safely with negligible dose to workers, patients, and family members. Methods:  Yttrium-90 was prepared as insoluble (yttrium phosphate) microparticles in a phosphate-buffered saline (PBS) solution mixed with a polymer composite (hydrogel) carrier for direct intra-tumoral injection. Privately owned cats, dogs, and horses presenting with soft-tissue sarcomas were treated at several veterinary clinics to demonstrate safety, best placement methods, and most effective treatment doses. Results: Upon injection using multiple parallel-needles, the carrier solution warmed and gelled in situ--forming a solid matrix that entrapped the Y-90 microparticles and prevented out-migration via blood circulation. Co-registered PET/CT imaging post-injection confirmed uniform placement in target tissues. Each subject exhibited an objective response to therapy; best results were associated with smaller tumors treated at higher doses (300 to 400 Gy). Treated animals experienced no radiation-related illness or adverse tissue reactions. Therapeutic ratios achieved ranged from 200:1 upwards to 10000:1. Complete tumor destruction was confirmed by histopathology.  Conclusions:  Some tumors represent poor candidates for surgical excision or cannot be treated using external beams for curative therapy. However, direct intra-tumoral injection of Y-90-microparticles in a polymer composite matrix provides a safe, efficient, high-dose therapy, with tumor cell killing associated with localized dose. Results of this research confirm the opportunity for multiple oncology applications in both human and veterinary patients.

CiteFisher DR, Korenko MK. High-dose precision radionuclide therapy (PRnT) by direct interstitial injection: optimizing therapeutic ratios for safe and effective delivery of high-dose radionuclide therapy in treating solid tumors. GHPA Technical Meeting, Tbilisi, Georgia, 3 Nov. 2023. Available at: