Interstitial Therapy of Feline Sarcoma using an Injectable Y-90-Polymer Composite (Radiogel)

Objectives: Yttrium-90-polymer-composite (radiogel) may be administered directly into cancerous tissues to deliver highly localized beta radiation for therapy. In a dose-escalation study, we investigated the feasibility of treating feline sarcomas as a model for non-resectable solid tumors in man and animals to gain clinical experience and to identify optimal methods for placing the composite uniformly within target tumor tissue.

Methods: The resorbable hydrogel delivery vehicle for the Y-90-(YPO₄) particles comprised a sterile, phosphate-buffered saline (PBS) solution containing a dissolved co-polymer of PLGA (poly-(DL-lactic acid-co-glycolic acid)) and PEG (poly-(ethylene glycol)) at 30 weight-percent. Prior to therapy, the hydrogel was added to a small amount of PBS containing a calibrated Y-90 activity within insoluble, high-purity yttrium-phosphate (YPO₄) particles (nominally 1-3 µm dia.), and was well-mixed. The composite was injected into sarcoma tissue of four cats (one more pending) with 25-27 gage needles under ultrasound guidance using a parallel-needle grid pattern and approximate 5-mm spacings. The cats were anesthetized for the procedure with Desflurane. After injection, the solution (10-15% by tumor volume) gelled within interstitial spaces to solid phase at body temperatures approaching 37°C to contain the activity intratumorally. The cats were then placed in a radiation isolation room and monitored overnight. Planned imaging with CT was performed at 2-weeks prior to injection, immediately post-injection, and then again at 3-weeks and 6-weeks post-injection.

Results: Gelation within extracellular spaces held the Y-90-YPO₄ particles in place without migration from the tumor to deliver a planned radiation absorbed dose (100 to 300 Gy) to target tissue through complete decay. Post-injection, the cats exhibited some pain in the tumors, and all had decreased appetites for 3-6 weeks post injection. At the 3-week recheck in three cats, the tumors remained stable in size. One cat was euthanized at that recheck due to health concerns unrelated to the treatment, and the tumor was harvested for examination. In one other cat, the tumor was successfully removed at the 6-week time point. In two cats, tumor removal had not yet occurred. Response of the tumor tissue to Y-90 radiation therapy post-removal was evaluated by pre-histological analysis. A definitive correlation was observed on histopathology between necrosis of tumor and sites of composite injection.

Conclusions: Our clinical team demonstrated successful placement of Y-90-polymer composite without measurable external radiation dose to any staff. The radiogel carrier materials performed as expected before and after injection. The cat patients recovered quickly from the procedure but may have experienced pain and loss of appetite related to nerve damage from needle injections. Tumors showed objective response with indications of tumor cell destruction associated with localized radiation. Support: Washington State Life Sciences Discovery Fund