The effect of antibody protein dose on the uniformity of tumor distribution of radioantibodies: An autoradiographic study

Summary The inaccessibility of radiolabeled antibody to poorly vascularized regions of solid tumors may reduce the therapeutic efficacy of these macromolecules. Theoretical mathematical models have predicted that increasing the protein dose administered would reduce the heterogeneity of radioantibody distribution. This investigation was undertaken to evaluate this hypothesis in experimental animal models. We have utilized the technique of macroautoradiography to demonstrate an increase in tumor penetration of the lower-affinity¹²⁵I-labeled NP-4 or higher-affinity Immu-14 anti-carcinoembryonic antigen (anti-CEA) mAbs into small (60.25—0.4 g) and large (0.8–1.5 g) GW-39 and LS174T human colonic xenografts, grown subcutaneously in the nude mouse, when 400 µg unlabeled antibody is administered simultaneously with 10 µg (100 µCi) radioantibody. Further increases in protein to 800 µg result in a reduction in total tumor uptake of the antibody. These differences in mAb distribution could be visualized as early as 1 day after antibody injection. Improved mAb penetration was also achieved for the Mu-9 anti-CSAp (anti-mucin) antibody using 800 µg unlabeled antibody. An irrelevant antibody (AFP-7-31) was found to be homogeneously distributed 3 days after injection, even at a low protein dose. Attempts to improve mAb penetration by increasing the protein dose in the GS-2 colorectal tumor, a model that has low NP-4 accretion as a result physiological barriers separating antibody from antigen, were not successful. These results suggest that a more homogeneous distribution of radioantibody can be achieved by carefully selecting a dose of unlabeled antibody to coadminister. Work is currently in progress to determine the effect of improved tumor distribution of radioantibody on the therapeutic potential of a single dose of radioantibody.This work has been supported in part by USPHS grants CA-37895, CA 39841, and RR-05 903 (Division of Research Resources), National Institutes of Health, Department of Health and Human ServicesResearch fellow of the Dutch Cancer Society     

Plant Traces Resembling Skolithos

The ichnogenus Skolithos Haldeman 1840 is a simple tubular trace fossil that was initially described as a “fucoid” or seaweed impression, i.e., a fossilized marine plant. Today the tracemaker is commonly considered to have been a vermiform marine invertebrate, although this interpretation is not acceptable to all. It is the name giver to the archetypal, Seilacherian Skolithos ichnofacies, which is a widely acknowledged indicator of relatively high energy, shallow water, nearshore to marginal marine environments. Here we record and describe analogous cylindrical structures, unquestionably reflecting plant tracemakers. These have been recognized in Quaternary consolidated “coffee” sandrock and Recent coastal dune, marsh or swamp, and salt meadow settings from northern New Zealand and Sapelo Island, USA.

We conclude that Skolithos is not an unequivocal indicator of shallow marine settings. Our observations confirm the opinions of a number of previous workers who have expressed the need for caution when using this ichnotaxon as a shallow-water, higher energy palaeoenvironmental indicator, especially when supporting evidence is otherwise lacking. In particular we note that in high intertidal and non-aquatic settings, Skolithos may be a plant trace fossil rather than serve as evidence for invertebrate activities. At the present time there is pressing need for a thorough systematic revision of the Skolithos ichnotaxon.