Model based calculation for effective cancer radioimmunotherapy.
The major problem of tumour radioimmunotherapy remains the low tumour antibody uptake and this leads to inadequate tumour irradiation. The antibody characteristics which influence uptake have been identified and quantified previously using a non-linear compartmental model that simulates antibody distribution to tumour and body after intravenous injection. The model has now been extended, in combination with MIRD dosimetry tables, to calculate the integral tumour/body radiation dose for a range of antibody masses (1, 10 and 50 mg), sizes (binding site fragments and whole molecules) and affinities (K = 10(9)-10(13) mol-1). Antibody requirements for delivering 60 Gy to the tumour over 11.6 days were calculated for 131I and 90Y-labelled antibodies and included the effect of widely varying dose rates. The model predicted that intact antibodies of high affinity (10(11)-10(13) mol-1) produced effective tumour radiation doses with acceptable whole body radiation levels. By contrast, antibody fragments gave higher body radiation levels and required larger injected activity because of renal excretion. The model predicted higher therapeutic indices for 90Y-labelled antibody compared with 131I.
Attard
A R
AR
Department of Immunology, University of Birmingham Medical School, UK.
Chappell
M J
MJ
Bradwell
A R
AR
D000915:Antibody Affinity; D006801:Humans; D007128:Immunoglobulin Fragments / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D018448:Models, Immunological; D008962:Models, Theoretical; D009369:Neoplasms / Q000532:radiotherapy*; D011829:Radiation Dosage; D016499:Radioimmunotherapy / Q000379:methods*; D011879:Radiotherapy Dosage; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics
D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D015021:Yttrium Radioisotopes