Despite therapeutic advances made in the last decade, there remains a high unmet need for new cancer treatments. Radiation therapy is a proven approach to treating many cancers and is typically administered by an external beam of high energy rays. In contrast, radiopharmaceuticals selectively deliver radioisotopes to tumors via the bloodstream.
Radiopharmaceuticals have the unique advantage of being both diagnostic and therapeutic. The same drug conjugate could be used for both diagnostic imaging and therapeutic use by switching out the radioisotope. Direct visualization of drug conjugate uptake by tumors with imaging allows for proper patient selection to receive the therapeutic radioisotope (e.g. Actinium-225).
Validated solid tumor targets
Numerous tumor targets have been clinically validated but have yet to be pursued as radiopharmaceuticals. A systematic evaluation was conducted by RayzeBio to identify biologically-relevant, tumor-specific targets suitable for targeted radiotherapy. These targets have high expression on solid tumors with little to no expression on normal tissues.
Binders to target
Several criteria are critical when considering delivery of a radioactive isotope. Molecular binders need to be designed to provide exquisite affinity and specificity to tumor targets to minimize off-target effects. At the same time, the binders should be small and agile to allow for deep tumor penetration and be tunable to create drug-like properties for proper clearance from the bloodstream.
Focused on therapeutics
Multiple therapeutic radioisotopes have the potential to be potent agents of therapeutic efficacy. Actinium-225 is an alpha emitting radioactive particle that has high energy density acting at distances of just a few cell widths. At these short distances, radiation can be restricted to the cancer cells of interest with minimal risk to nearby normal healthy tissue.