Transcatheter pseudo-vascular isolation for localization and concentration of a large molecule theranostic probe into a transgenic OncoPIG kidney tumor

Abstract

Introduction

Great strides have been made identifying molecular and genetic changes expressed by various tumor types. These molecular and genetic changes are used as pharmacologic targets for precision treatment using large molecule (LM) proteins with high specificity. Theranostics exploits these LM biomolecules via radiochemistry, creating sensitive diagnostic and therapeutic agents.

Intravenous (i.v.) LM drugs have an extended biopharmaceutical half-life thus resulting in an insufficient therapeutic index, permitting only palliative brachytherapy due to unacceptably high rates of systemic nontarget radiation doses to normal tissue.

We employ tumor arteriole embolization isolating a tumor from the systemic circulation, and local intra-arterial (i.a.) infusion to improve uptake of a LM drug within a porcine renal tumor (RT).

Methods

In an oncopig RT we assess the in vivo biodistribution of ^99mTc-labeled macroaggregated albumin (MAA) a surrogate for a LM theranostics agent in the RT, kidney, liver, spleen, muscle, blood, and urine. Control animals underwent i.v. infusion and experimental group undergoing arteriography with pseudovascular isolation (PVI) followed by direct i.a. injection.

Results

Injected dose per gram (%ID/g) of the LM at 1 min was 86.75 ± 3.76 and remained elevated up to 120 min (89.35 ± 5.77) with i.a. PVI, this increase was statistically significant (SS) compared to i.v. (13.38 ± 1.56 and 12.02 ± 1.05; p = 0.0003 p = 0.0006 at 1 and 120 min respectively). The circulating distribution of LM in the blood was less with i.a. vs i.v. infusion (2.28 ± 0.31 vs 25.17 ± 1.84 for i.v. p = 0.033 at 1 min). Other organs displayed a trend towards less exposure to radiation for i.a. with PVI compared to i.v. which was not SS.

Conclusion

PVI followed by i.a. infusion of a LM drug has the potential to significantly increase the first pass uptake within a tumor. This minimally invasive technique can be translated into clinical practice, potentially rendering monoclonal antibody based radioimmunotherapy a viable treatment for renal tumors.