Kinetic modelling for distribution and removal of plasma proteins with altered biological behaviour in vivo

Abstract

Ever since the introduction of radioiodinated tracers for turnover kinetic investigations on plasma protein metabolismin vivo, concern has been expressed about possible changes of some biological properties capable of altering the metabolic behaviour of the tracers with respect to the native proteins1. In fact, virtually all the procedures devised for radioiodination involve exposing the proteins to some oxidising agent, for the introduction of radioiodine in the tyrosyl residues. Furthermore, the process of protein purification itself before labelling may induce some conformational changes capable of altering the biological behaviourin vivo, such as polymerisation, or loss of some sugar moiety, etc. The injection of a radioiodinated tracer protein of inadequate quality into the subjects under study almost invariably results in a much faster drop in the plasma disappearance curve with respect to an undamaged tracer (with the noticeable exception of proteins such as insulin, where the damaged tracer shows prolonged survival rates, probably due to defective receptorial interaction). Thus, the calculation methods commonly used for the sets of experimental data lead to erroneous evaluations of the degradation rates and of the distribution parameters of the tracer. Empirical procedures have been used in the past to assess the effects of various iodination techniques and of various degrees of iodination on the metabolic properties of tracers in vivo (as, for instance, in the case of human serum albumin), based on the variations of the daily fractional catabolic rate, or on the ratio between the sum of the catabolic rates during the first 3 days of the study and the sum of the catabolic rate values over the -entire experimental interval from day 1 to day 62–4.