Response to motexafin gadolinium and ionizing radiation of experimental rat prostate and lung tumors.
OBJECTIVE
To investigate the responses of two experimental rat tumors to single and fractionated X-ray doses whether or not combined with Motexafin gadolinium (MGd), and the distribution of MGd in R3327-MATLyLu (MLL) tumors using MRI.


METHODS
L44 lung tumor in BN rats and MLL prostate tumor in Copenhagen rats were grown subcutaneously. MGd at concentrations of 8.7 to 25.1 micro mol/kg was administered 2 h before or just before treatments with single and fractionated X-ray doses. Tumor volume growth delay was the endpoint used. The two-dimensional distribution of the MGd concentration in time was analyzed simultaneously in slices through the center of MLL tumors using MRI. Directly after the MRI experiments, tumor sections were stained for cytoplasm, nuclei, and microvessel endothelium.


RESULTS
MGd at different concentrations administered a few minutes or 2 h before X-ray doses produced no radiation enhancement in the two tumor models. The MGd concentration as determined by MRI was maximal 5 min after injection and decreased slowly thereafter. In a representative section at the center of the MLL tumor, the microvessel density is nearly homogeneous and correlates with a nearly homogeneous MGd distribution. Hardly any MGd is taken up in underlying muscle tissue.


CONCLUSIONS
No radiosensitization was observed for the different irradiation regimens. The distribution of MGd is nearly homogeneous in the MLL tumor and hardly any MGd is taken up in underlying muscles. Our negative results on radiosensitivity in our two tumor models raise questions about the efficacy of MGd as a general radiosensitizing agent.
Dehnad
Homan
H
Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands. H.Dehnad@radcl.ruu.nl
Kal
Henk B
HB
Stam
Tanja
T
Gademan
Iris S
IS
van Moorselaar
R Jeroen A
RJ
van der Sanden
Boudewijn P J
BP
D000818:Animals; D001835:Body Weight / Q000528:radiation effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D008665:Metalloporphyrins / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D051381:Rats
D008665:Metalloporphyrins; D011838:Radiation-Sensitizing Agents; C437683:motexafin gadolinium