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Drug Design Reviews - Online (Discontinued)


ISSN (Print): 1567-2697
ISSN (Online): 1567-2697

Effects of Adjuvant Chelator or Chemotherapy on Dosimetry of 90Y-CC49 in Lung Cancer Patients Using 111In-CC49 as a Tracer

Author(s): R. F. Meredith, S. Shen, F. Robert, M. B. Khazaeli, D. G. Elliott, D. Carey, W. Wang, D. J. Macey, J. Schlom and A. F. LoBuglio

Volume 1, Issue 4, 2004

Page: [333 - 339] Pages: 7

DOI: 10.2174/1567269043390645

Price: $65


Dosimetry estimates of normal organs and tumors are presented for 34 lung cancer patients after administration of 111In-CC49 tracer / 90Y-CC49 + / - adjuvant EDTA or DTPA chelator, or paclitaxel chemotherapy. Data were obtained from quantitation of serial gamma camera images and blood radioactivity. Radiation dose estimates were calculated by Medical Internal Radiation Dose (MIRD) formalism using lesion or organ dimensions obtained from CT images. The pharmacokinetics and dosimetry of the serum and whole body after a single IV administration of 90Y-CC49 were similar to that reported in multiple studies of 131I-CC49 (serum T1 / 2 45 + / - 15h), with a ∼2-fold range between the shortest and longest circulation time. Normal organs including liver, lung and kidney had ranges from 5-7 fold between the lowest and highest radiation dose while tumors had the widest range of 10 fold. Using specific liver masses for 20 patients resulted in dose estimates 0.5-1.7x that derived with the mass of a standard reference man model. Whole body radiation dose per unit of injected activity (cGy / mCi) was relatively consistent among 33 patients, varying between 2.0 and 2.6 with a mean of 2.4 despite modest but significant differences with chemotherapy or chelator. Paclitaxel in conjunction with the 90Y-CC49 resulted in a modest increase in whole body cGy / mCi but effects for other parameters measured were not statistically significant. The adjuvant use of EDTA or DTPA as a chelator for unbound radioactive metal resulted in small, although significant decreases, in whole body T1 / 2, and cGy / mCi for the whole body, lung and liver but did not significantly change plasma pharmacokinetics.

Keywords: antibody, radioimmunotherapy, lung cancer, and dosimetry

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