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     

Comment on Baylor: A Note About Dreams of Scientific Problem Solving

Creative problem-solving dreams virtually always occur only after the dreamer has done extensive work on the issue awake. Most typically, a person is stuck at one particular step of a multiple phase process and the dream solves that step. The dream of Dmitri Mendeleev about The Periodic Table of the Elements is no exception. All accounts of this event agree that he'd worked for years on the Table, produced other drafts, but that he attributed the version he was most satisfied with to a dream. It is less clear whether Kedrov is correct in his reconstruction that it was the reversal of columns vs. rows which the dream provided. Accounts of dreams from contemporary scientists and inventors are a richer source for the detail required to generalize about the role of dreams in problem solving.     

EATB Donor Case Workshop 2007

The European Association of Tissue Banks (EATB) Donor Case Workshop is a forum held within the programme of the EATB annual Congress since 2003. This workshop has been used to discuss clinical donor cases with peer review of practice. It was agreed in advance that the experience of the 2007 workshop should be shared by publication as an example of participative learning which can be extended to other fields within tissue banking and which may be applicable in other disciplines. The EATB Congress in 2008 will extend the idea of participative open workshops with two additional workshops, one on Quality System cases and another on heart valve cases.