Division of Nuclear Medicine, University of Massachusetts Medical School, Worcester, MA01655-0243, United States.
Eur J Cancer. 2009 Nov;45(17):3098-103. doi: 10.1016/j.ejca.2009.09.007. Epub 2009 Oct 5.
Our previous studies have indicated that the optimal dosage ratio of pretargeting antibody to effector is proportional to their maximum percent tumour accumulations (MPTAs). This study quantitatively describes how both MPTAs and their ratio change with tumour size, to simplify pretargeting optimisation when tumour size varies. The CC49 antibody dosages below saturation of the tumour antigen level were first examined for the LS174T tumour mouse model. Then the MPTAs of the antibody in mice bearing tumours of different sizes were determined, always at antibody dosages below antigen saturation. Historical data from this laboratory were used to collect the MPTAs of the (99m)Tc-cMORF effector for different tumour sizes, always at effector dosages below that required to saturate the MORF in tumour. The MPTAs versus tumour sizes for both the antibody and the effector were fitted non-linearly. The best fit of the antibody MPTA (Y(antibody)) with tumour size (x) in grams was Y(antibody)=19.00 x(-0.65) while that for the effector was Y(effector)=4.51x(-0.66). Thus, even though the MPTAs of both vary with tumour size, the ratio (Y(antibody)/Y(effector)) is a constant at 4.21. In conclusion, the MPTA ratio of the antibody to the effector was found to be constant with tumour size, an observation that will simplify pretargeting optimisation because remeasurement of the optimum dosage ratio for different tumour sizes can be avoided. Theoretical considerations also suggest that this relationship may be universal for alternative antibody/effector pairs and for different target models, but this must be experimentally confirmed.
我们之前的研究表明，前靶向抗体与效应物的最佳剂量比与它们的最大肿瘤积累百分比（MPTA）成正比。本研究定量描述了 MPTA 及其比值如何随肿瘤大小而变化，以便在肿瘤大小变化时简化前靶向优化。首先在 LS174T 肿瘤小鼠模型中检查了 CC49 抗体剂量是否低于肿瘤抗原水平的饱和。然后，在抗体剂量低于抗原饱和的情况下，确定了不同大小肿瘤小鼠中抗体的 MPTA。来自本实验室的历史数据用于收集不同肿瘤大小的（99m）Tc-cMORF 效应物的 MPTA，始终在效应物剂量低于肿瘤中 MORF 饱和所需的剂量下进行。抗体和效应物的 MPTA 与肿瘤大小呈非线性拟合。抗体 MPTA（Y(antibody)）与肿瘤大小（x）的最佳拟合是 Y(antibody)=19.00 x(-0.65)，而效应物的最佳拟合是 Y(effector)=4.51x(-0.66)。因此，尽管两种药物的 MPTA 都随肿瘤大小而变化，但比率（Y(antibody)/Y(effector)）在 4.21 时是一个常数。总之，抗体与效应物的 MPTA 比值与肿瘤大小呈常数关系，这一观察结果将简化前靶向优化，因为可以避免为不同肿瘤大小重新测量最佳剂量比。理论考虑还表明，这种关系可能对替代抗体/效应物对和不同的靶模型具有普遍性，但这必须通过实验来证实。
