Lars-Erik Nilsson

Application of accelerator mass spectrometry (AMS) for high-sensitivity measurements of 14CO2 in long-term studies of fat metabolism

Long-term measurements of 14C in CO2 expired after ingestion of 14C-labelled triolein were performed using accelerator mass spectrometry (AMS). About 30% of a given amount of 14C-labelled triolein was catabolized rapidly, while the remaining 70% had a very slow turnover. The study shows the potential of the AMS technique for the study of the long-term biokinetics of 14C-labelled pharmaceuticals. The AMS technique allows the administered activity to be reduced by several orders of magnitude without compromising the study. It may also allow studies of rare drug metabolites.

Antithrombin III concentrate: its catabolism in health and in antithrombin III deficiency

The catabolism of purified radiolabelled antithrombin III (AT III) concentrate was studied in two normals and two patients with congenital AT III deficiency both alone and combined with warfarin. The radiolabelling with iodine monochloride did not change the quality of the concentrate. The half-life varied between 3.4 and 4.8 days. No difference between normals and patients with congenital deficiency in non-acute stage could be observed in the catabolic parameters; nor was there any influence with warfarin.

AMS studies of the long-term turnover of -labelled fat in man

Abstract To estimate the biokinetics of 14 C -labelled fatty acids and the associated radiation absorbed dose to man, long-term retention of 14 C from oral intake of glycerol tri[1- 14 C ]oleate (triolein) has been studied using accelerator mass spectrometry (AMS). As a complement to earlier reported data for three individuals, we present here results for one person from measurements up to 4.6 yr after administration, now also including 14 C -levels in fat, muscle and bone. In this subject, a total of 44% of the administered activity was recovered in the exhaled air. Fasting increased the exhalation of 14 C . The “excess” 14 CO 2 due to fasting had a half-life of about 400 d. AMS measurements on fat, muscle and bone biopsies taken from the same subject 4.5 yr after ingestion indicated that a small fraction of the administered activity was still present in fat. Also, bone tissue had a higher 14 C specific activity than the current environmental level. No significantly increased level was found in the muscle sample.

A programme for long-term retention studies of 14C-labelled compounds in man using the Lund AMS facility

Abstract Organic compounds labelled with 14C are routinely and widely used in clinical medicine and biomedical research. There are, however, considerable uncertainties in the current estimates of the absorbed doses to the body from 14C-labelled radiopharmaceuticals. In this paper a project is described using accelerator mass spectrometry (AMS) to perform investigations of the long-term biokinetics of 14C from various 14C-labelled pharmaceuticals in man. The use of the AMS technique makes it possible to follow the turnover of the radionuclide administered for extensive periods and also to decrease the activity administered.

Properties and catabolism of heat treated antithrombin III concentrate

Heat treatment is employed to diminish the transmission of hepatitis when blood products are administered. It is possible that such a procedure could reduce the biological activity of the proteins and induce changes in structure and aggregation state. We have therefore made in vitro and pharmacokinetic studies of heat treated antithrombin III (AT III) concentrate using both radiolabelled and non-labelled preparations. The purification, heat treatment and the radiolabelling procedures did not induce any changes in the AT III molecules with exception of a decrease in heparin affinity in about 10% of the molecules. The in vivo studies using 125I AT III showed that the fractional catabolic rate was increased and the half-life was shortened by about 20-25% compared to our previous studies on non-heat treated AT III concentrate. Our present findings indicating a mean half-life of 3.0 days are quite comparable to studies by others on non-heat treated AT III, however.