ABSTRACT
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.
Subject(s)
Breast Neoplasms/diagnosis , Contrast Media , Manganese , Metalloporphyrins , Animals , Dose-Response Relationship, Drug , Female , Humans , Magnetic Resonance Imaging , Mice , Mice, Nude , Transplantation, HeterologousSubject(s)
Contrast Media , Magnetic Resonance Imaging , Manganese , Metalloporphyrins , Porphyrins , Animals , Breast Neoplasms/diagnosis , Contrast Media/administration & dosage , Humans , Injections, Intraperitoneal , Mice , Mice, Nude , Porphyrins/administration & dosage , Transplantation, HeterologousABSTRACT
The criteria for tumor-specific MRI contrast agents are considered. The metalloporphyrins have been shown to be potential tumor-specific contrast agents due to their selective retention by cancer cells. The Mn(III) water-soluble porphyrin complexes are preferred on the basis of relaxivity and stability. Protein binding in human plasma enhances the relaxivity of Mn(III)-tetraphenylsulfonato-porphyrin (MnTTPS). In preliminary work this agent was shown to enhance MRI contrast at 0.5 T in subcutaneous human colon carcinomas grown in nude mice. Here we report further evidence of enhanced contrast in the same system, and extend this work to human breast tumors in nude mice using a 2 T animal imager. Questions of metalloporphyrin stability, toxicity and dose-contrast relationship are discussed.
Subject(s)
Breast Neoplasms/diagnosis , Contrast Media , Magnetic Resonance Imaging , Porphyrins , Animals , Humans , Mice , Mice, Nude , Transplantation, HeterologousABSTRACT
Murine hybridoma cell lines were developed which synthesized monoclonal antibodies against Actinobacillus actinomycetemcomitans-associated antigens. Monoclonal antibodies specific for an antigen(s) common to all A. actinomycetemcomitans isolates tested but not detected on other gram-negative oral plaque microorganisms or other Actinobacillus species were identified. Monoclonal antibodies specific for each serotype group of A. actinomycetemcomitans which did not bind to other Actinobacillus species or oral plaque microorganisms were also identified.
