In vivo animal studies with gadolinium (III) texaphyrin as a radiation enhancer.
OBJECTIVE
Gadolinium texaphyrin (Gd-Tex, PCI-0120) is an expanded porphyrin that has demonstrated radiation enhancement. In this study, we evaluated the radiation enhancement and biolocalization of Gd-Tex in three animal tumor models.


METHODS
EMT6, SMT-F, and MCa tumors were established intramuscularly or subcutaneously. Gd-Tex and other metallotexaphyrins were administered prior to single or multiple fractions of radiation. 14C-labeled Gd-Tex was used for biolocalization studies.


RESULTS
Gd-Tex, in combination with radiation, produced significant tumor growth delay compared to irradiated control groups in both single and multifraction radiation studies. Gd-Tex radiation enhancement was observed only when the drug was given before, but not after irradiation. Several metallotexaphyrins, identical except for the metal ion, were studied in the EMT6 tumor model including gadolinium (Gd), lutetium (Lu), europium (Eu), yttrium (Y), and cadmium (Cd) texaphyrin complexes. Only Gd-Tex produced radiation enhancement. Biodistribution studies using 14C-labeled Gd-Tex demonstrated drug selectivity and retention in tumors growing intramuscularly compared to uninvolved muscle and plasma.


CONCLUSIONS
Gd-Tex produces reproducible radiation enhancement in a variety of in vivo tumor models. This drug's unique radiochemistry, tumor selectivity, and in vivo activity suggests possible mechanisms of action not addressed by in vitro assay methods.
Miller
R A
RA
Pharmacyclics, Inc., Sunnyvale, CA 94086-4521, USA.
Woodburn
K
K
Fan
Q
Q
Renschler
M F
MF
Sessler
J L
JL
Koutcher
J A
JA
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004307:Dose-Response Relationship, Radiation; D004354:Drug Screening Assays, Antitumor; D008665:Metalloporphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000532:radiotherapy; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011853:Radiobiology; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D008665:Metalloporphyrins; D011838:Radiation-Sensitizing Agents; C437683:motexafin gadolinium