Image-guided Polymeric Nanomedicines for Radiochemotherapy

Drug targeting systems are nanometer-sized carrier materials designed for improving the biodistribution of systemically applied (chemo-) therapeutics. Reasoning that I) the temporal and spatial interaction between i.v. applied weekly chemotherapy and clinically relevant daily radiotherapy is suboptimal, and that II) drug targeting systems are able to improve the temporal and spatial parameters of this interaction, we have recently set out to evaluate the potential of 'carrier-based radiochemotherapy'.

HPMA copolymers were used as a model drug targeting system, doxorubicin and gemcitabine as model drugs, and the syngeneic and radio- and chemoresistant Dunning AT1 rat prostate carcinoma as a model tumor model. Magnetic resonance imaging, gamma-scintigraphy, fluorescence microscopy and HPLC were used to evaluate the biodistribution and the tumor accumulation of the copolymers, and clinically relevant regimens of radiotherapy and chemotherapy to evaluate their efficacy-enhancing effects.

First, the polymeric drug carriers were shown to circulate for prolonged periods of time, to localize to tumors both effectively and selectively, and to improve the tumor-directed delivery of low molecular weight agents. Subsequently, they were then shown to interact synergistically with radiotherapy, with radiotherapy increasing the tumor accumulation of the copolymers, and with the copolymers increasing the therapeutic index of radiochemotherapy (both for doxorubicin and for gemcitabine).

Based on these findings, and on the fact that its principles are likely broadly applicable, we propose 'carrier-based radiochemotherapy' as a novel concept for improving the treatment of advanced solid malignancies.

Lernziele:

• Drug targeting

• Nanomedicine

• Image-guided drug delivery

• Theranostics

• Radiochemotherapy

Korrespondierender Autor: Lammers T

Helmholtz-Institut, RWTH Aachen, Experimentelle Molekulare Bildgebung, Pauwelsstrasse 30, 52074 Aachen

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