Optimal preloading in radioimmunotherapy with anti-CD45 antibody
Anterior and posterior γ-camera images 24 h post injection of the first (A) and the second (B) measurement series (patient 3) using 111In-labeled anti-CD45 antibody. The second image (B, without preloading) shows higher accumulation of labeled antibody in the liver and spleen and less in the red marrow. Although a considerable portion of antibody of the first administration is still bound to the liver and spleen, for 1 mg of antibody sufficient antigens sites are available for rapid binding.
PBPK model of unlabeled antibody. The injected antibody (main vascular compartment) is distributed according to the blood flow to the organs. The antibody binds to anti-CD45 expressing cells. Bound antibody degrades with the same rate in each organ. The fragments of the bound antibody move into the delay compartment (delay) and are then released into the blood (MetaP). Unbound antibody moves into the extra vascular compartment (Ex) and then into the blood (MetaP). The complete model consists of two circulating systems (one for labeled and one for unlabeled antibody) which are connected by the competition for the same number of antigens in the organs and by the physical decay (Ref. 5). Lu denotes lung, n = nodes, and v = vascular.
Data of both measurement series of patient 2 and corresponding fits using the AICc best model.
Prediction and measurements of therapeutic serum curve.
Ratios of residence time of red marrow and liver (patient 1) with varying preload of unlabeled antibody determined by using either both data series or only the first measurement series.
Administered amounts of anti-CD45 antibody and activities.
Adjusted R2 and fitted parameters of best model.
Prediction accuracy of 90Y serum residence times τserum and residence times τi for optimal versus standard preloading.
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