Yttrium-90 (90Y)-polymer composite (RadioGel™) is a new cancer therapeutic agent for treating solid tumors by direct interstitial injection. The 90Y-composite comprises insoluble, microscopic yttrium-phosphate particles carried by a sterile, injectable water-polymer (hydrogel) solution that can be placed directly by needle injection into solid tumors. The yttrium-90-RadioGel™ agent was designed to provide a safe, effective, localized, high-dose beta radiation for treating solid tumors. The properties of 90Y-RadioGel™ also make it a relatively safe agent for health care personnel who prepare, handle, and administer the material. The purpose of this work was to demonstrate and characterize radiation safety of the injectable 90Y-RadioGel™ therapeutic agent. Safety in the patient is defined by its ability to target precisely and remain confined within tumor tissue so that radiation doses are imparted to the tumor and not to normal organs and tissues. Radiation safety for health care personnel is defined by the low radiation doses received by persons who prepare and administer the agent. These safety features were demonstrated during experiments, first involving laboratory rabbits and second in cat and dog animal patients that were treated clinically for sarcoma tumors. This paper focuses mainly on the rabbit tissue biodistribution study; follow-on clinical application in cat and dog subjects confirmed the rabbit results. Implanted VX2 liver tumors in the hind limbs of 26 New Zealand White rabbits were treated using tracer amounts of either (a) 90Y-RadioGel™ or (b) 90Y-microparticles in phosphate-buffered saline (PBS) without the gel carrier. Tumor and margin injections were interstitial. Rabbits were euthanized at 48 h or 10 d following injection. Blood and tissues (tumor or tumor margins, liver, lymph nodes, rib bone, kidney, spleen) were collected for liquid scintillation counting using wet-ash procedures. Biodistribution was also analyzed at 10 d post-injection using micro-computed tomography. Thirteen cat and dog subjects were also treated clinically for sarcomas. Liquid scintillation counting at 48 h post-injection of tumors or margins with 90Y-RadioGel™ showed that significant radioactivity was measurable only at the site of administration and that radioactivity above detector background was not found in blood or peripheral organs and tissues. At 10 d post-injection, microCT showed that yttrium phosphate microparticles were confined to the injection site. Yttrium-90 remained where placed and did not migrate away in significant amounts from the injection site. Radiation doses were confined mainly to tumors and margin tissues. During preparation and administration, radiation doses to hands and body of study personnel were negligible. This work showed that 90Y-RadioGel™ can be safely prepared and administered and that radiation doses to cancer patients are confined to tumor and margin tissues rather than to critical normal organs and tissues.

Extravasation during radiopharmaceutical injection may occur with a frequency of more than 10%. In these cases, radioactivity remains within tissue and deposits unintended radiation dose. Characterization of extravasations is a necessary step in accurate dosimetry, but a lack of free and publicly available tools hampers routine standardized analysis. Our objective was to improve existing extravasation characterization and dosimetry methods and to create and validate tools to facilitate standardized practical dosimetric analysis in clinical settings. Using Monte Carlo simulations, we calculated dosimetric values for sixteen nuclear medicine isotopes: 11 C, 64 Cu, 18 F, 67 Ga, 68 Ga, 123 I, 131 I, 111 In, 177 Lu, 13 N, 15 O, 82 Rb, 153 Sm, 89 Sr, 99m Tc, and 90 Y. We validated our simulation results against five logical alternative dose assessment methods. We then created three new characterization tools: a worksheet, a spreadsheet, and a web application. We assessed each tool by recalculating extravasation dosimetry results found in the literature and used each of the tools for patient cases to show clinical practicality. Average variation between our simulation results and alternative methods was 3.1%. Recalculation of published dosimetry results indicated an average error of 7.9%. Time required to use each characterization tool ranged from 1 to 5 min, and agreement between the three tools was favorable. We improved upon existing methods by creating new tools for characterization and dosimetry of radiopharmaceutical extravasation. These free and publicly available tools will enable standardized routine clinical analysis and benefit patient care, clinical follow-up, documentation, and event reporting.