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Transcatheter pseudo-vascular isolation for localization and concentration of a large molecule theranostic probe into
Samuel L Rice1, Fernando Gómez Muñoz2, Jamaal Benjamin3
1Netherlands Cancer Institute-Antoni van Leeuwenhoekziekenhuis, Department of Radiology, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands; UT Southwestern Medical Center, Department of Radiology, Interventional Radiology Section, 5959 Harry Hines Blvd., Dallas, TX 75390-9061, Professional Office Building I (HP6.600) Mail Code 8834, United States of America.
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.
Insights
Pseudovascular isolation (PVI) with intra-arterial infusion significantly enhances large molecule (LM) drug uptake in renal tumors compared to intravenous infusion. This minimally invasive technique shows promise for improving radioimmunotherapy for kidney cancers.
Area of Science:
- Oncology
- Radiochemistry
- Interventional Radiology
Background:
- Precision medicine utilizes molecular targets for targeted therapies.
- Theranostics combines diagnostic and therapeutic agents using large molecule (LM) biomolecules.
- Intravenous LM drugs have limitations due to poor therapeutic index and systemic radiation exposure.
Purpose of the Study:
- To evaluate the efficacy of pseudovascular isolation (PVI) and intra-arterial (i.a.) infusion for improving LM drug delivery to renal tumors (RT).
- To assess the biodistribution of a LM theranostics surrogate in a porcine RT model using PVI and i.a. infusion versus intravenous (i.v.) infusion.
Main Methods:
- Oncopig renal tumors (RT) were used to assess in vivo biodistribution of 99mTc-labeled macroaggregated albumin (MAA) as an LM theranostics surrogate.
- Animals received either i.v. infusion (control) or arteriography with PVI followed by direct i.a. injection (experimental group).
- Biodistribution was measured in the RT, kidney, liver, spleen, muscle, blood, and urine at 1 and 120 minutes post-injection.
Main Results:
- Intra-arterial PVI resulted in significantly higher LM uptake in the RT (86.75 ± 3.76% ID/g at 1 min) compared to i.v. infusion (13.38 ± 1.56% ID/g; p=0.0003).
- LM levels in the blood were significantly lower with i.a. PVI (2.28 ± 0.31%) versus i.v. infusion (25.17 ± 1.84%; p=0.033 at 1 min).
- A trend towards reduced radiation exposure in other organs was observed with i.a. PVI, though not statistically significant.
Conclusions:
- PVI followed by i.a. infusion significantly enhances first-pass tumor uptake of LM drugs.
- This minimally invasive approach holds potential for clinical translation.
- It may establish monoclonal antibody-based radioimmunotherapy as a viable treatment for renal tumors.
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