MRI contrast-dose relationship of manganese(III)tetra(4-sulfonatophenyl) porphyrin with human xenograft tumors in nude mice at 2.0 T.
Previously we reported that Mn(III)tetra(4-sulfonatophenyl) porphyrin, MnTPPS4, is a contrast agent which can effectively enhance tumor detection by MRI. By imaging 30 additional athymic nude mice bearing subcutaneous MCF-7 WT human breast carcinoma xenografts, we have extended dose-contrast relationships over a wide range of intraperitoneal (IP) doses ranging from 0.025 to 0.50 mmol/kg. The benefits of IP injection are higher possible doses on a volume basis and a reduction in toxicity versus IV administration. Full coronal cross-section images have been obtained on a 2-T spectrometer. Although individual tumor masses displayed different distribution patterns, reflective of their internal morphology, single doses of 0.10 mmol/kg or greater were necessary to produce a detectable effect. At a dose of 0.50 mmol/kg, marked enhancement was produced. Multiple small dosages administered over the course of several days before imaging did not produce increased enhancement. Preliminary results on the new porphyrin derivative, MnTPPS3, indicate that the ratio of the toxic dose to the effective dose may be adjustable to render this class of agents clinically useful.
Place
D A
DA
Department of Pharmacology, Georgetown University Medical Center, Rockville, MD 20850.
Faustino
P J
PJ
Berghmans
K K
KK
van Zijl
P C
PC
Chesnick
A S
AS
Cohen
J S
JS
D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis*; D003287:Contrast Media; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008345:Manganese; D008665:Metalloporphyrins; D051379:Mice; D008819:Mice, Nude; D014183:Transplantation, Heterologous
D003287:Contrast Media; D008665:Metalloporphyrins; D008345:Manganese; C056661:manganese(III)tetraphenylporphine sulfonate