Limits of sensitivity for the radioimmunodetection of colon cancer by means of a hand held gamma probe.

This study was undertaken to define the limits for the radioimmunodetection of minimal deposits of colorectal cancer cells using a hand held gamma probe. 125I labeled monoclonal antibody 17-1A and its F(ab')2 fragments were reacted in vitro with cells of the human colorectal cancer line SW 1116. The limits of sensitivity of the probe were determined by injecting doubling dilutions of 125I-antibody coated SW 1116 cells ranging from 10(7) to 3.9 x 10(4) subserosally at 2 cm intervals into 60 cm segments of freshly obtained autopsy or surgical specimens of human colon. A linear relationship was observed between the number of cells injected and the number of counts obtained with either the probe or well counter. As few as 6.25 x 10(5) 125I-antibody coated cells (less than 1 mm3) were detected under experimentally defined conditions by an earlier version of the probe, and 3.9 x 10(4) coated cells (much less than 1 mm3) could be detected by the currently available model. Although the count rates were less than 5% of those obtained by well counter, nevertheless, these were 10-25 times greater than background and allowed the detection of tumor cell deposits that otherwise would not have been discernible by either palpation or external scintigraphy. These findings, in conjunction with ongoing clinical studies, suggest that the hand held gamma probe may increase the usefulness of monoclonal antibodies for the radioimmunodetection of cancer.

Effects of calcium glucarate on the promotion of diethylnitrosamine-initiated altered hepatic foci in rats.

Calcium glucarate (CGT), an inhibitor of beta-glucuronidase, is a potent inhibitor of chemically-induced tumors when administered orally. The present study was undertaken to determine the effects of CGT on the promotion of hepatocarcinogenesis by phenobarbital following initiation with diethylnitrosamine (DENA). Partially hepatectomized, DENA-initiated female Sprague-Dawley rats, previously maintained only on chow diet for 2 months, were supplemented with either 0.05% phenobarbital alone or 0.05% phenobarbital plus 4% dietary CGT, for varying time intervals up to 6 months. Histopathologic evaluation of the liver sections showed that CGT significantly delayed the development of altered hepatic foci (AHF). By the seventh month post-initiation, however, the frequency and severity of changes seen in the livers of experimental animals approximated those of the controls.

Phenotypic diversity of murine B16 melanoma detected by anti-B16 monoclonal antibodies.

A panel of monoclonal antibodies (MoAbs), produced against the murine B16 melanoma, has been used to characterize its phenotypic diversity. Six MoAbs that did not bind to primary cultures of kidney, brain or liver, spleen cells, thymocytes, 3T3 fibroblasts, melanin, or transferrin receptors were selected for further evaluation. Five MoAbs, which recognized surface antigens expressed on parental B16 cells and the B16-F1, B16-F10, B16-F10 FLR, and B16-BL6 sublines, did not appear to cross-react with each other, suggesting that they identified antigenically distinct epitopes. Four MoAbs, designated as IB16-2, IB16-4, IB16-8, and IB16-10, recognized B16 surface antigens that were variably expressed over short periods of time. This variable expression was independent of the cell cycle and was characteristic of four B16 sublines. Two of these MoAbs, both of the IgG2b isotype, fixed rabbit and guinea pig complement and were cytolytic in the presence of rabbit complement. One MoAb, designated IB16-6, recognized a surface antigen consistently expressed on greater than 90% of cells of both the parental tumor and the sublines. This MoAb bound to several murine and one human melanoma cell line, but not to other histopathological types of tumors or normal tissues. The cellular antigen that this antibody recognized was not detected in the cytoplasm, did not modulate in the presence of IB16-6, and was sensitive to trypsin, pronase, alcohols, acetone, and detergents, thereby suggesting that it was a protein. Our data are among the first that directly show the extent of phenotypic diversity of the B16 melanoma and sublines that have been derived from it.