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Ex vivo correlation of antigen expression with uptake of ¹²⁴I-huA33 in humans

¹ Radiology; ² Medical Physics; ³ Surgery, MSKCC, New York, New York; ⁴ LICR, New York, New York

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Objectives: Compare the ex vivo uptake of a radiolabeled antibody with the tissue antigen expression.

Methods: All studies were performed under an IRB approved protocol and only patients scheduled for surgery were included. Patients, with known colon cancer disease, were injected with 4-10 mCi of ¹²⁴I-huA33 (10 mg huA33) and imaged with a clinical PET scanner at 4-6 days post injection. After PET imaging, the patients underwent surgery and the tumor masses were removed. Portions of the tumor and normal tissue samples were counted in a gamma counter and tissue membranes prepared. The membranes were assayed for protein content and then used in saturation binding studies with ¹³¹I-huA33 to determine the numbers of receptors present and the antibody/antigen binding affinity (experimental control). The data were plotted as the ¹²⁴I-huA33 uptake (%ID/g) against the A33 antigen expression (pmoles/mg protein).

Results: 24 tumor and 26 normal samples were obtained from 8 patients. The plot of the tumor uptake against antigen expression was linear with a slope of 77 nmoles/%ID (R² 0.65). The plot of the normal uptake against antigen expression was linear with a slope of 105 nmoles/%ID (R² = 0.62). Despite the differing sampling times (for 5 to 8 days) there were no significant differences for the individual data (slopes of 72, 79 and 82 nmoles/%ID for 5, 6 and 8 days respectively).

Conclusions: This study shows that, for the non internalizing A33 antigen, the tissue uptake of ¹²⁴I-huA33 is directly proportional to the tissue expression of A33. We also found little variation between 5 and 8 days post injection. The data is now being correlated with the PET derived uptake values.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Smith-Jones, P. Articles by Larson, S. PubMed Articles by Smith-Jones, P. Articles by Larson, S.