Bertil Nosslin

Studies in pharmacokinetics and tolerance of substances temporarily retained in the liver by microsphere embolization.

Earlier investigation has shown that a temporary arrest of arterial blood flow can be achieved by embolization with degradable microspheres. This study was made to investigate the change in pharmacokinetics and drug tolerance which takes place when a substance is retained in the liver by a microsphere embolization. 14C-labelled inulin and 5-fluoro-uracil were studied. The administration of these substances with microspheres led to a delay in their systemic distribution. Furthermore there was an increased tolerance to 5-fluoro-uracil, probably due to a prolonged first pass effect when the substance was temporarily retained in the liver by a microsphere embolization.

Effective dose equivalent from radiopharmaceuticals

The concept of “effective dose equivalent”, which was introduced by the International Commission on Radiological Protection (ICRP) for occupationally exposed workers, has also created the possibility of expressing by means of a single figure, the radiation risk to patients undergoing different medical radiodiagnostic procedures. In this study, we present the effective dose equivalent for various nuclear-medicine investigations. The figures given are primarily based on a review of data contained in the literature on the mean absorbed dose to various organs. In many cases, however, our own calculations, using biokinetic data derived from the literature, have been used.It was found that for the different radiopharmaceuticals, the effective dose equivalent per activity unit administered extends over an interval of five orders of magnitude, from 0.00015 to 20 mSv/MBq. For the technetium-labelled compounds, the absorbed dose for 90% of the substances lies within the narrower interval between 0.0060 and 0.025 mSv/MBq. With the aid of the figures presented, each nuclear medicine department will be able to estimate the effective dose equivalent and, hence, the risk to patients undergoing different investigation.

Is CEA analysis of value in screening for recurrences after surgery for colorectal carcinoma

The progress of 139 patients operated upon for cure of colorectal carcinoma, was followed postoperatively with a standardized protocol. A CEA test was performed for comparison with other parameters. Median observation time was four years. When an upper limit for CEA of 7.5 μg/l was allowed, sensitivity was found to be 78 per cent, specificity 91 per cent, and predictive value of an elevated CEA concentration, 83 per cent. In general, CEA measurement traced, recurrence six months before clinical diagnosis. In only a few cases was recurrence first heralded by an abnormality in other blood chemistry test results. CEA may thus be used in postoperative screening for recurrence even though most recurrences, when detected, are not curable.

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.

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.

Whole body measurements of sodium turnover in offspring of patients with sustained essential hypertension

The elimination rate (percent per day) of injected 22Na using a whole body measurement technique was significantly lower (5.8±1.5) in normotensive or borderline hypertensive offspring of essential hypertensive patients than in 15 age- and sex-matched, normotensive controls (7.3±1.0). There were no significant differences in exchangeable sodium, whole body potassium or in the urinary excretion of sodium, potassium and creatinine. The basis for the difference in turnover rate during week 1 is probably an alteration in the cellular handling of sodium (i.e. increased intracellular sodium) in the still normotensive offspring of patients with essential hypertension.The long-term (more than 100 days) whole body retention of 22Na was found to be only 0.1% of that injected, which justifies the use of this method on larger population groups.

Quantitative analysis of the distribution of 99mTc-labelled ethylene hydroxy diphosphonate in young rats

The distribution of 99mTc-labelled ethylene-1-hydroxy-1,1-diphosphonate (EHDP) in young rats was studied 1, 3, 6 and 9 h after intraperitoneal injection. The concentration of 99mTc in bone was 8–10 times higher than that in the kidnnys and 20–1000 times higher than those in other soft tissues. The concentration in bone remained constant throughout the observation time. In some of the animals sacrificed after 3, 6, or 9 h the uptake in the liver and spleen was higher than that found in the majority of the animals.

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.