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Department of Pathology and Oncology, University of Kansas Medical Center, College of Health Sciences and Hospital, Kansas City, Kansas 66103
In this series of experiments, we have studied the distribution patterns of 99mTc-labeled Corynebacterium parvum in normal and tumor-bearing mice. C57BL/6 mice were given i.v., i.p., or s.c. injections of 250 µg of 99mTc-labeled C. parvum and killed at 10 min, 1, 4, and 24 hr. After i.v. administration, labeled organisms were distributed primarily to the liver, the lungs, and the blood (46% of injected dose), followed by the gastrointestinal tract, the spleen, and the kidneys (11%). Total recoverable radioactivity, which was defined as the percentage of injected dose that was recovered, ranged from 59% at 10 min to 15% at 24 hr. In contrast to this, 99mTcS colloid, an inert particulate material, was localized almost entirely in the liver, and the amount recoverable remained constant over 24 hr. One hr after i.p. administration of 99mTc-labeled C. parvum, the gastrointestinal tract accounted for 27% of the injected radioactivity, followed by liver, blood, and spleen (12%). This was rapidly excreted between 4 and 24 hr, at which time only 12% of the injected dose was recovered. The skin accounted for 54.6% of the injected radioactivity 1 hr after s.c. injection, 6% 4 hr after s.c injection, and 0.8% at 24 hr after s.c. injection. Eight percent of the recoverable radioactivity was detected in the lymph nodes at 1 hr and by 24 hr this had increased to 50%. Total recoverable radioactivity was 68% at 1 hr, 31.6% at 4 hr, and 8.5% at 24 hr. The distribution of i.v.-administered C. parvum in C57BL/6 mice that carried the B16 melanoma was similar to that in normal animals, although the amount localized in liver was somewhat less. The tumor itself accounted for 8.7% of the recoverable radioactivity at 1 hr and increased to 39% at 24 hr. After intralesional injection, the tumor accounted for 25% of the injected radioactivity and 58% of the recoverable radioactivity at 1 hr, and this increased to 28% of the injected radioactivity and 85% of the recoverable radioactivity at 24 hr. Although the immunopotentiating activity of C. parvum in tumor-bearing hosts may be attributable primarily to a generalized effect on the reticuloendothelial system, localization and retention of the organisms within the tumor itself also may have some relationship to its immunotherapeutic effectiveness.
1 Supported by Grants CA 16503-03 and GM 22814-01 from the NIH. Presented in part at the Sixty-first Annual Meeting of the Federation of American Societies for Experimental Biology, Chicago, Ill., April 4 to 8, 1977 (23).
2 To whom requests for reprints should be addressed, at Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Milwaukee, Wis. 53201.
Received 6/27/77. Accepted 9/27/77.
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