Abstract
1802
Objectives: A major concern in using therapeutic radionuclides is the radiation exposure to whole-body, blood-forming organs (red marrow, spleen), gonads (testes, ovaries), and effective dose equivalent based on clinical doses. Therefore, the delivery method of such radionuclides plays an important role in the feasibility of its use in humans. This study aimed to characterize the degradation profile of an alginate hydrogel and determine acute toxicity in tumor-bearing animals in order to assess its usefulness for cancer radiochemotherapy.
Methods: Hydrogel was prepared by mixing sodium alginate (5% soln) with calcium chloride (5% soln) and vortexing. The degradation profile was evaluated by placing the hydrogel in conical tubes filled with DMEM and incubated at 37oC. Samples (n=3/time point) were collected on day 2, 7, 14 and 21, lyophilized and weighed. Prostate tumor-bearing mice (n=15/group) were injected with hydrogel, 188Re, 188Re-hydrogel and 188Re-cisplatin-hydrogel intratumorally, and sacrificed on day 2, 7, 10 and 14 to determine renal and systemic toxicity, along with reduction in tumor burden.
Results: The degradation profile demonstrated no significant change in the dry weight of the hydrogel at 21 days post-incubation and visual inspection showed the complex to remain intact. Hematology and complete blood chemistry from animals treated with 188Re showed systemic and renal toxicity, while groups given radio- or radiochemotherapy in the presence of hydrogel showed less side effects. 188Re provided a slight delay in tumor growth, while greater anti-tumor effects were achieved with 188Re-hydrogel and 188Re-cisplatin-hydrogel.
Conclusions: An in situ hydrogel has been developed for local retention of 188Re and slow-release of cisplatin. The hydrogel is stable and capable of retaining radioactive and chemotherapeutic materials at 7 days post-injection. Systemic toxicity associated with 188Re-hydrogel may be attributed to leakage from the injection site and can be improved with the use of an automated injection device.
- Society of Nuclear Medicine, Inc.