Direct Interstitial Treatment of Solid Tumors Using an Injectable Yttrium-90-Polymer Composite.

Abstract

Purpose: Yttrium-90 (90Y)-polymer composite (radiogel) may be administered directly into cancerous tissues to deliver highly localized beta radiation for therapy. In a dose-escalation study, the authors investigated the feasibility of treating feline and canine soft-tissue sarcomas as a model for nonresectable solid tumors in humans to gain clinical experience and to identify optimal methods for placing the composite uniformly within target tumor tissue.Materials and Methods: Five cats (Washington State University) and three dogs (University of Missouri) were selected for treatment from among veterinary clinic patients presenting with subcutaneous soft-tissue sarcomas. The therapeutic radiogel composite comprised two parts that were combined before therapy: (1) a calibrated activity of highly insoluble 90Y(YPO4) particles in a sterile, phosphate-buffered saline solution and (2) a resorbable hydrogel delivery vehicle containing a dissolved copolymer of poly-(DL-lactic acid-co-glycolic acid) and poly-(ethylene glycol). Sarcomas of anesthetized animals (five cats and three dogs) were injected with the 90Y-radiogel (10%–15% by tumor volume) using a parallel-needle grid pattern with ∼4–5-mm spacings with or without ultrasound guidance. After injection, the composite solution gelled within tumor interstitial spaces to solid phase upon reaching body temperatures to constrain the 90Y activity intratumorally. The animals were then imaged with computed tomography (CT) or positron emission tomography (PET)/CT and placed in radiation isolation for overnight monitoring and follow-up.Results: Gelation of the composite within tumor extracellular spaces confined the 90Y(YPO4) particles in place to deliver a planned radiation absorbed dose (100–320 Gy) to target tissue through complete decay. Response of the tumor tissue to 90Y-radiation therapy postexcision was evaluated by imaging, tumor resection, and histology. Correlation was observed on histopathology between tumor destruction and radiation dose. With uniform placement at high dose, the authors achieved complete remission or stable disease (at 1–2 months posttreatment).Conclusions: This study demonstrated successful injection of 90Y-polymer composite (radiogel) without discernable radiation dose to normal organs or other detrimental side effects. Animal patients recovered quickly from the injection procedure. The better therapeutic responses were observed at mean doses at or above 300 Gy.