Paul O. Scheibe

Requirements for a treatment planning system for radioimmunotherapy

Cancer-seeking antibodies carrying radionuclides can, in theory, be very powerful agents for the radiotherapy of cancer. However, as with all radiotherapy, the undesired dose to critical normal organs is the limiting factor that determines success or failure. The distribution of radiation dose in cancer and noncancer tissue is highly dependent on choices the therapist can make: choices of the antigens to be targeted, choices of the antibodies or antibody fragments to be used, choices of radionuclides, of amounts, of timing, and other electives. New technologies, especially of monoclonal antibody production, make the options myriad. Optimization of this therapy depends on a foreknowledge of the radiation dose distributions to be expected. The necessary data can be acquired by established tracer techniques, in individual patients, for particular treatment selections. These tracer techniques can now be implemented by advanced equipment for quantitative, tomographic radionuclide imaging and strengthened by dynamic modeling of the physiological parameters which govern radionuclide distribution, and hence radiation dose distribution.

Identifiability Analysis of an In Vivo Receptor-Binding Radiopharmacokinetic System

A five-state, nonlinear model describing the pharmacokinetics of a receptor-binding radiopharmaceutical is presented. Local parameter identifiability analysis was performed preexperimentally to investigate the chemical and observational conditions required for adequate estimates of hepatic blood flow, receptor-ligand affinity, and receptor population. The ability to estimate the above parameters from externally observed kinetic data depended upon receptor-ligand affinity, the molar dose of the radiopharmaceutical, the number and coupling of the observers, and independent knowledge of the coupling coefficients or ligand-receptor affinity.

Goodness-of-fit and local identifiability of a receptor-binding radio-pharmacokinetic system

A four-state nonlinear model describing a radiopharmacokinetic system for a hepatic receptor-binding radiopharmaceutical, (/sup 99m/Tc)-galactosyl-neoglycoalbumin, (TcNGA), was tested for goodness-of-fit and local identifiability using scanning data from nine healthy subjects and seven patients with severe liver disease. Based on standard deviations of liver and heart imaging data at equilibria as a measure of observational error, the reduced chi-square ranged from 0.5 to 2.6. Values above 1.2 occurred when the subject moved during the 30 min study. Relative standard errors for each parameter were determined. The highest standard errors occurred when the amount of TcNGA injected exceeded the total amount of receptor. Therefore, when TcNGA functional imaging was performed without excess patient motion and receptor saturation, the kinetic model provided data fits of low systematic error and yielded high precision estimates of receptor concentration and forward binding rate constant.<<ETX>>

Statistical profiles in computed tomography.

A diagnostic console consisting of a high resolution video display coupled to a microcomputer was programmed to enable us to derive a battery of statistical parameters from any area of interest on a CT scan. These statistical parameters enable us to characterize the CT numbers of areas of interest in a more meaningful way than has been possible with most currently available consoles. A combination of statistical parameters enables us to discriminate between certain lesions with similar appearance such as porencephalic cysts, epidermoid tumors and cystic gliomas.