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Abstract of Proposed Work (Page 151-a), Subject: Direct Measurement of Absorbed Dose for Radioimmunotherapy

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PROJEl! B:Direct Measurement of Absorbed Dose f o r With t h e development of the hybridam technology, the production of highly specific tumor associated monoclonal antibodies has provided new optimism for the ad juv ant delivery of therapeutic radiation doses via radioimmunotherapy. This effort has been for the most part led by members of the nuclear medicine and immunology scientific carmunities. Bio distribution data generated by these investigators regarding the therapeutic efficacy using radiolabeled antibodies has been expressed i n terms (Le., percent injected dose (activity) / gram, localization index and antibody affinity constant) that are not readily interpretable In a radiation tk rap y physics or radio biological framework (i.e. absorbed radiation dose, dose =.ate, +amor grarth delay and control). We propose to use a modified form of the well - established TL dosimetry technology t o measure the dose resulting from radioinmulnotherapy experiments i n tumor bearing mice and normal dogs. We have designed and tes bda miniature caSaQ:Dy implantation of the dosimetry in a n animal model undergoing radio labeled antibody therapy. Direct measurement of absorbed dose from beta and gamma radiation i n the M l s may be obtained upon removal af the dosimeter a t mimal sacrifice o r by surgery. The anti - ferr it in antibody to hepatom Ln rats developed by the Johns Hopkins University w i l l make an ideal moc+l for this i n vivo work. Bone marrow and whole body doses may also ti assessed in dogs for toxicity studies. These data my then be rela:-? t o antibody affinity and location data obtained by vitro cell = in ding tests and serial bio distribution studies. Autoradiographs of tumor section will be anaiyzed by the micro-TLD technique i n terms of absorbed dose. Efforts will also be made to characterize the radiobiclogical dose response of the hepatoma tumors by external beam irradiation, administered alone and i n combination wit ! radiolabeled antibody then?:/. With the compilation of this dosimetric and r q dio biological data ba;e i n animal models, a rational foundation of estimating the therapeb4trc efficacy of adjuvant Box No. OF I,