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Estimation of Monoclonal Antibody-associated ⁹⁰Y Activity Needed to Achieve Certain Tumor Radiation Doses in Colorectal Cancer Patients¹

Division of Diagnostic Radiology, Department of General Oncologic Surgery, Division of Radiation Oncology, City of Hope National Medical Center, and Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010

In these measurements, we quantitated, via surgical samples, human primary tumor uptake of the anti-carcinoembryonic antigen monoclonal antibody T84.66. Uptake was measured in units of percentage of injected dose/kg with ¹¹¹In as the radiolabel. All 11 colorectal lesions were nonnecrotic and were visualized upon scanning. Tumor volume was calculated using the three orthogonal dimensions as described by pathology. Uptake mean ± SD was 6.55 ± 3.55% injected dose/kg with a range of 1.2 to 10.4% injected dose/kg. Lesion mean volume was 36 cm³ with a range of 1.5 to 304 cm³. Using mean values, assuming no biological clearance and that the biodistribution of the monoclonal is independent of its radiolabel, the predicted human tumor ⁹⁰Y ß dose was 0.12 Gy/mCi. Therefore a 10-Gy tumor dose would require 83 mCi of i.v. activity. Using least and highest uptake results, requisite activity values were 3-fold larger and smaller respectively. Thus, there was approximately an order of magnitude variation in the amount of ⁹⁰Y predicted to achieve a given tumor dose in colorectal cancer patients. Murine and human uptake values were consistent if lesion mass and carcinoembryonic antigen content were taken into account.