Truncation of blood curves to enhance imaging and therapy with monoclonal antibodies

Targeting of monoclonal antibody (Mab) to solid tumor sites is a function o f the blood curve of activity versus time. It has been suggested that the b lood curve be artificially reduced to approach zero so that the contrast be tween tumor and blood uptake is maximized. We analyzed tumor uptake as a fu nction of the time t(c) of blood curve truncation. By using a convolution a pproach, we were able to find the optimal times for setting the blood curve to zero in either diagnostic or therapeutic animal examples. Two iodinated cT84.66 anti-CEA engineered fragments, diabody and minibody, were consider ed using previous data from nude mouse studies involving the LS174T colorec tal tumor model. Figures of merit (FOMs) were used to compare ordinary and truncated blood curves and their associated tumor accumulations. Using a I- 123 label, it was seen that the appropriate time for diagnostic truncation occurred when tumor uptake, as measured, was a maximum. The corresponding p oint for therapy (with I-131 as a label) was at infinite time. We also demo nstrated that the use of traditional indices led to ambiguities in the choi ce of truncation times. The traditional therapy index, the ratio of the int egral of the tumor uptake to the integral of the blood uptake, was found to be a numerical constant independent of t(c). This ratio was proved to be t he integral of the tumor impulse response function. Use of such convolution techniques to assess truncation of the perfused material is probably also applicable to multistep processes as well as to lesion targeting with other tumor-specific pharmaceuticals. (C) 2000 American Association of Physicist s in Medicine.