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Title of Journal: Pharm Res

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Abbravation: Pharmaceutical Research

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Springer US

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DOI

10.1016/0141-6359(93)90012-y

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1573-904X

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Biodistribution and Efficacy of Low TemperatureSe

Authors: Ashish Ranjan Compton J Benjamin Ayele H Negussie Saurin Chokshi Paul H Chung Dmitry Volkin Nitin Yeram W Marston Linehan Matthew R Dreher Peter A Pinto Bradford J Wood
Publish Date: 2016/06/24
Volume: 33, Issue: 10, Pages: 2459-2469
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Abstract

Female athymic nude mice with human prostate PC3 Mluciferase cells grown subcutaneously into the right hind leg were randomized into six groups saline +/− heat free docetaxel +/− heat and LTSL docetaxel +/− heat Treatment 15 mg docetaxel/kg was administered via tail vein once tumors reached a size of 200300 mm3 Mice tumor volumes and body weights were recorded for up to 60 days Docetaxel concentrations of harvested tumor and organ/tissue homogenates were determined by LCMS Histological evaluation Mean vessel density Ki67 proliferation Caspase3 apoptosis of saline free Docetaxel and LTSL docetaxel +/− heat n = 3–5 was performed to determine molecular mechanism responsible for tumor cell killingLTSL/heat resulted in significantly higher tumor docetaxel concentrations 47fold greater compared to free docetaxel Adding heat to LTSL Docetaxel or free docetaxel treatment resulted in significantly greater survival and growth delay compared to other treatments p  005 Differences in body weight between all Docetaxel treatments were not reduced by 10 and were not statistically different from each other Molecular markers such as caspase3 were upregulated and Ki67 expression was significantly decreased in the chemohyperthermia group Vessel density was similar post treatment but the heated group had reduced vessel area suggesting thermal enhancement in efficacy by reduction in functional perfusion

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