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Biotech / Medical : Pharmacyclics (PCYC) -- Ignore unavailable to you. Want to Upgrade?

To: Icebrg who wrote (697)	1/18/2004 11:51:25 AM
From: scaram(o)uche	Read Replies (1) \| Respond to of 717

(editing, here..... Marc, I meant to address this post to you, just to let you see that there is controversy.... Erik knows such, didn't want to imply that I was imparting anything new.) Int J Radiat Oncol Biol Phys. 2003 Nov 1; 57(3): 787-93. Response to motexafin gadolinium and ionizing radiation of experimental rat prostate and lung tumors. Dehnad H, Kal HB, Stam T, Gademan IS, van Moorselaar RJ, van der Sanden BP. Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands. PURPOSE: 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. CONCLUSION: 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. and the traditional "alert!" reference...... Cancer Res. 2000 Jan 1; 60(1): 86-91. Re-evaluating gadolinium(III) texaphyrin as a radiosensitizing agent. Bernhard EJ, Mitchell JB, Deen D, Cardell M, Rosenthal DI, Brown JM. University of Pennsylvania, Department of Radiation Oncology, Philadelphia 19104, USA. bernhard@mail.med.upenn.edu Gadolinium(III) texaphyrin (Gd-tex) was recently proposed as a radiosensitizing agent that combines preferential tumor uptake with detection of drug localization by magnetic resonance imaging (S. W. Young et al., Proc. Natl. Acad. Sci. USA, 93: 6610-6615, 1996). In view of the initial report on this compound, four radiobiology laboratories undertook independent efforts to further study radiosensitization by Gd-tex. In addition to repeating the previously reported studies on Gd-tex in HT-29 cells, we tested five other human tumor cell lines (U-87 MG, U251-NCI, SW480, A549, and MCF-7). These studies included a Gd-tex treatment period of 24 h before irradiation (as in the original publication), with concentrations of Gd-tex ranging from 20-500 microM. In neither the HT-29 cells nor any of the other five human cell lines did we see radiation sensitization by Gd-tex. Two cell lines (MCF-7 and U-87 MG) were further tested for radiosensitization by Gd-tex under hypoxic conditions. No radiosensitization was observed in either case. Finally, the radiation response of two tumor lines were assessed in vivo. Neither HT-29 xenografts in severe combined immunodeficient (SCID) mice nor RIF-1 tumors growing in C3H mice demonstrated radiosensitization after Gd-tex treatment before single or fractionated doses of radiation. Our results raise questions about the efficacy of Gd-tex as a radiosensitizing agent.