Radiobiology Issues Regarding Theranostic Radiopharmaceuticals
J O'Donoghue1*, M Cremonesi2*, R Hernandez3*, Z Morris4*, (1) Memorial Sloan-Kettering Cancer Center, New York, NY, (2) European Institute of Oncology IRCCS, Milano, Lombardia, IT, (3) University of Wisconsin-Madison, Madison, WI, (4) University of Wisconsin School of Medicine and Public Health, Madison, WI
Presentations
TU-K-202-0 (Tuesday, 7/12/2022) 4:30 PM - 6:00 PM [Eastern Time (GMT-4)]
Room 202
Currently there is intense interest in radiopharmaceutical therapy (RPT), particularly in terms of a theranostic paradigm that incorporates both diagnostic and therapeutic elements. Typically, this consists of matched pairs of radiolabeled molecules; a diagnostic partner (labeled with a positron- or single photon-emitting radionuclide) that provides information about disease extent and phenotype and serves to predict the utility of a therapeutic partner (usually labeled with a beta- or alpha-particle-emitting radionuclide) that delivers target-specific ionizing radiation.
RPT is fundamentally a systemic treatment and tumor targets may be widely dispersed throughout the body. Individual lesions may differ in size, from macroscopic tumors visualizable by clinical imaging, to microscopic deposits too small to be seen. Radiation-induced toxicities are generally off-target and normal tissues at risk (e.g., bone marrow, kidney, salivary glands) may be far from the sites of disease.
In RPT, absorbed dose distributions are driven by biological function and non-uniformities may be produced by the combination of non-uniform activity distributions and the ranges of ionizing particles emitted by therapeutic radionuclides. Particle ranges can extend from centimeter scales, for high-energy beta-particles, to cellular or sub-cellular scales for alpha particles or Auger electrons. In addition, RPT doses are generally delivered at a low and decreasing dose-rate. These complexities may be further compounded by differences in radiation quality.
Learning Objectives:
1. Understand the fundamental features of the theranostic paradigm
2. Understand the key radiobiological differences between RPT and external beam radiotherapy in terms of clinical targeting, dose-rate, dose non-uniformity, and LET
3. Understand what goes into designing a radiopharmaceutical and how its radiobiological potency can be optimized
4. Recognize the impact of novel radiobiological mechanisms for RPT, such as immunological/abscopal factors.
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