Truncation of blood curves to enhance imaging and therapy with monoclonal antibodies.
Targeting of monoclonal antibody (Mab) to solid tumor sites is a function of the blood curve of activity versus time. It has been suggested that the blood curve be artificially reduced to approach zero so that the contrast between tumor and blood uptake is maximized. We analyzed tumor uptake as a function of the time tc of blood curve truncation. By using a convolution approach, 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 considered using previous data from nude mouse studies involving the LS174T colorectal tumor model. Figures of merit (FOMs) were used to compare ordinary and truncated blood curves and their associated tumor accumulations. Using a 1231 label, it was seen that the appropriate time for diagnostic truncation occurred when tumor uptake, as measured, was a maximum. The corresponding point for therapy (with 1311 as a label) was at infinite time. We also demonstrated that the use of traditional indices led to ambiguities in the choice of truncation times. The traditional therapy index, the ratio of the integral of the tumor uptake to the integral of the blood uptake, was found to be a numerical constant independent of tc. This ratio was proved to be the 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.
Williams
L E
LE
Division of Radiology, City of Hope National Medical Center, Beckman Research Institute, Duarte, California 91010, USA. lwilliams@coh.org
Liu
A
A
Wu
A M
AM
Yazaki
P J
PJ
Yamauchi
D M
DM
Lopatin
G
G
Raubitschek
A A
AA
Wong
J Y
JY
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000627:therapeutic use*; D055592:Biophysical Phenomena; D001703:Biophysics; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000532:radiotherapy; D016719:Radioimmunodetection; D016499:Radioimmunotherapy; D019275:Radiopharmaceuticals / Q000097:blood* / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D019275:Radiopharmaceuticals