OPTIMAL TUMOR TARGETING BY ANTIBODIES - VALIDATION OF A MATHEMATICAL-MODEL

A nonlinear compartmental model has been developed to optimise tumour targeting using radiolabelled antibodies. The model has been simulated using the computer package FACSIMILE incorporating published parameter values. Model validation has been carried out using data from 6 patients with colorectal cancer, all of whom had 2 anti-CEA scans using a monoclonal antibody labelled with technetium-99m. Patients initially had a small dose of antibody labelled with 450 MBq and blood samples collected over the following 24 hours. The patients were scanned at the end of that period. A larger dose of antibody was then administered with the same technetium dose and the patients were rescanned after a further 24 hours. The plasma count data and first scan uptake ratio values were then entered into the parameter fitting routine available within FACSIMILE. Parameter values for the known movement of antibody in the body were used to estimate the unknown parameter values to give a prediction of the second scan uptake ratio. The model gave a good prediction of the uptake ratio for the second scan. This procedure should enable prediction of the best dose for an optimal second scan and thereby improve tumour imaging using radiolabelled antibodies