Evaluation of Motexafin gadolinium (MGd) as a contrast agent for intraoperative MRI.
OBJECTIVE
The characteristics of an ideal contrast agent for use in the intraoperative MRI would be tumor-specificity and intracellular localization, combined with extended tumor enhancement, but with rapid elimination from the blood. The radiation sensitizing properties of Motexafin gadolinium (MGd) have been investigated in a number of clinical trials involving patients with brain metastases. These studies clearly show that MGd is detectable in magnetic resonance images many days following administration. The aim of this experimental study was to test whether Motexafin gadolinium (MGd) could serve as an efficient intraoperative contrast agent avoiding problems that arise with surgically induced intracranial enhancement.


METHODS
F98 orthotopic brain tumors or surgical lesions were induced in Fisher rats. T1-weighted MRI studies were performed with either a single or multiple daily doses of MGd. The last contrast dose was administered either 7 or 24 hours prior to scanning in both tumor-bearing or surgically-treated animals. All scans were T1-weighted nce (TR=495 ms; TE=1 ms.) with a slice thickness of 1.0 mm. Three tubes containing 2.3, 0.23 and 0.023 mg/mL of MGd (in physiological saline) respectively, were used as standards to calibrate the scans.


RESULTS
Animals receiving either 30 or 60 mg/kg MGd i.v. developed clinical signs of impaired motor activity, and increasing lethargy and were euthanized 48 hours after MGd administration due to their poor and deteriorating condition. MGd given i.p. was tolerated up to a dose of 140 mg/kg. Despite multiple dosages and several administration modes (i.p., i.v.) no significant enhancement was observed if the scans were performed 7 or 24 hours following the last MGd dose. Clear enhancement was seen though when the scans were performed 30 min following MGd administration, indicating that the agent was being taken up by the tumor. Scans of necrotic lesions though were positive though 7 hours following MGd injection. MGd scans had no significant enhancement following surgically-induced lesions while scans with conventional contrast agents showed both meningeal and intraparenchymal enhancement.


CONCLUSIONS
This study suggests that MGd is not sequestered in viable tumor for the necessary time interval required to allow delayed imaging in this model. The agent does seem to remain in necrotic tissue for longer time intervals. MGd therefore would not be suitable as a contrast agent in intraoperative MRI for the detection of remaining tumor tissue during surgery.
Hirschberg
H
H
Beckman Laser Institute, University of California, Irvine, CA 92612, USA. hirschberg@laser.bli.uci.edu
Wu
G N
GN
Madsen
S J
SJ
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D003287:Contrast Media / Q000493:pharmacokinetics / Q000633:toxicity; D004195:Disease Models, Animal; D004660:Encephalitis / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005910:Glioma / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D008665:Metalloporphyrins / Q000493:pharmacokinetics* / Q000633:toxicity*; D016343:Monitoring, Intraoperative / Q000379:methods*; D010775:Photic Stimulation; D010778:Photochemotherapy; D011237:Predictive Value of Tests; D051381:Rats; D011916:Rats, Inbred F344
D003287:Contrast Media; D008665:Metalloporphyrins; C437683:motexafin gadolinium