Abstract
CONCLUSION
Combining IA administration of a small-molecule radioprobe surrogate with embolization of the tumor's arterioles extending the time for interaction of the drug within the tumor by diminishing flow out of the tumor via the efferent capillaries significantly increases the first-pass uptake of the small-molecule drug within a tumor and decreases the radiation to normal nontumor tissues when compared with IV injection of the same drug. The minimally invasive drug delivery allows tumor-specific theranostic treatment of renal tumors with a brachytherapy-absorbed dose of radiation that is potentially curative.
RESULTS
18F-fluorodeoxyglucose (FDG) was used as a surrogate for a small-molecule theranostic agent in a porcine renal tumor model, this tumor model is not known to specifically express human tumor antigens, but the model demonstrates similar vascularity. Angiography and micron particle embolization of the tumor arterioles were performed in a renal tumor model. Significantly more tumor uptake (2-4×), was observed for intra-arterial administration (IA) compared to intravenous (IV) (%ID/g = 44.41 ± 2.48 vs. 23.19 ± 4.65; P = 0.0342 at 1 min and 40.8 ± 2.43 vs. 10.94 ± 0.42; P = 0.018 at 10 min). At later time points, up to 120 min after injection, washout of the tracer from the tumor was observed, but the percent injected dose per gram remained elevated, with three times higher concentration of FDG with IA administration compared with IV, but the difference was not statistically significant. A trend towards diminished systemic percent injected dose per gram measured in the blood, liver, kidney, spleen, muscle, and urine for study IA compared to IV administration is observed.
BACKGROUND
Small-molecule biomacromolecules target tumor-specific antigens. They are employed as theranostic agents for imaging and treatment. Intravenous small-molecule radioligands exhibit rapid tumor uptake and excretion. However, systemic administration for peptide receptor radionuclide therapy still lacks the therapeutic index to completely treat solid tumors beyond palliation. We study intra-arterial delivery with tumor embolization of a small molecule as a means to deliver local intertumoral brachytherapy for curative internal ablation.