Abstract
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, systemically administration for peptide receptor radionuclide therapy brachytherapy 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.
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 was performed in a renal tumor model. Significantly more, 2x to 4x more tumor uptake, for study intra-arterial. administration compared to i.v (%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* 10 min). At later time points, up to 120 mins after injection, washout of the tracer from the tumor was observed, but percent injected dose per gram remained elevated, with 3x higher concentration of FDG with intra-arterial administration compared to intravenous, but the difference was not statistically significant. Trend towards diminished systemic percent injected dose per gram measured in the blood, liver, kidney, spleen, muscle, and urine for study intra-arterial compared to intravenous administration.
Conclusion
Combining intra-arterial 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 SM drug within a tumor and decreased the radiation to normal non-tumor tissues when compared to intravenous 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.