Biomedical subjects

G Henriksen

Publications and source records attributed to G Henriksen.

9 recordsLinked to original sources

PubMed2006

Gender dependent rate of metabolism of the opioid receptor-PET ligand [18F]fluoroethyldiprenorphine.

AIM: The morphinane-derivate 6-O-(2-[(18)F]fluoroethyl)-6-O-desmethyldiprenorphine ([(18)F]FDPN) is a nonselective opioid receptor ligand currently used in positron emission tomography (PET). Correction for plasma metabolites of the arterial input function is necessary for quantitative measurements of [(18)F]FDPN binding. A study was undertaken to investigate if there are gender dependent differences in the rate of metabolism of [(18)F]FDPN. METHODS: The rate of metabolism of [(18)F]FDPN was mathematically quantified by fitting a bi-exponential function to each individual's dynamic metabolite data. RESULTS: No statistically significant gender differences were found for age, weight, body mass index or dose. However, significant differences (p < 0.01) in two of the four kinetic parameters describing the rate of metabolism were found between the two groups, with women metabolizing [(18)F]FDPN faster than men. These differences were found in the contribution of the fast and slow kinetic components of the model describing the distribution of radioactive species in plasma, indicating a higher rate of enzyme-dependent degradation of [(18)F]FDPN in women than in men. CONCLUSION: The findings reinforce the need for individualized metabolite correction during [(18)F]FDPN-PET scans and also indicate that in certain cases, grouping according to gender could be performed in order to minimize methodological errors of the input function prior to kinetic analyses.

Adult↗

PubMed2004

Proof of principle for the use of 11C-labelled peptides in tumour diagnosis with PET.

PURPOSE: The future significance of peptide radiopharmaceuticals in diagnostic imaging with PET will be dependent on methodological aspects, as well as other requirements such as availability of the radionuclide and cost-effectiveness of its production. The aim of this study was to evaluate whether recent improvements in the modification of peptide pharmacokinetics by carbohydration may open a niche for the use of 11C-labelled peptide receptor binding tracers. METHODS: A carbohydrated analogue of Tyr3-octreotate was used as a clinically relevant peptide. Oxime-mediated coupling between 4-[11C]methoxy-benzaldehyde and an aminooxy-conjugated peptide precursor provided the 11C-labelled peptide in 21+/-5% decay-corrected yield (n=4) in a synthesis time of about 1 h. RESULTS: In rat pancreas carcinoma xenografted mice, the compound displayed predominant and fast renal clearance combined with high tumour uptake (18.5+/-2.8% ID/g) at 30 min post injection. Corresponding values for kidney, liver and intestine were 18.5+/-2.4% ID/g, 3.2+/-0.5% ID/g and 2.1+/-0.3% ID/g, respectively. In a PET study with xenografted mice, the tumour (0.2-0.3 g) was clearly delineated as early as 20 min after injection. Somatostatin receptor (sstr)-specific uptake was demonstrated by reduction of tumour uptake to 20% of control by co-injection of TOC (0.4 mg/kg; 30 min p.i.). CONCLUSION: A 11C-labelled octreotate derivative has been prepared which shows suitable pharmacokinetics for in vivo imaging of sstr-overexpressing tumours and thus represents the first proof of principle for the potential of 11C-labelled peptides in tumour imaging.

Animals↗

PubMed2004

Synthesis and preclinical evaluation of the choline transport tracer deshydroxy-[18F]fluorocholine ([18F]dOC).

11C-labeled choline ([11C]CHO) and 18F-fluorinated choline analogues have been demonstrated to be valuable tracers for in vivo imaging of neoplasms by means of positron emission tomography (PET). The objective of the present study was to evaluate whether deshydroxy-[18F]fluorocholine, ([18F]dOC), a non-metabolizable [18F]fluorinated choline analogue, can serve as a surrogate for cholines that are able to be phosphorylated and thus allow PET-imaging solely by addressing the choline transport system. The specificity of uptake of [18F]dOC was compared with that of [11C]choline ([11C]CHO) in cultured rat pancreatic carcinoma and PC-3 human prostate cancer cells in vitro. In addition, biodistribution of [18F]dOC and [11C]CHO was compared in AR42J- and PC-3 tumor bearing mice. The in vitro studies revealed that membrane transport of both compounds can be inhibited in a concentration dependent manner by similar concentrations of cold choline (IC50 [18F]dOC= 11 microM; IC50 [11C]CHO=13 microM. In vitro studies with PC-3 and AR42J cells revealed that the internalized fraction of [18F]dOC after 5 min incubation time is comparable to that of [11C]CHO, whereas the uptake of [11C]CHO was superior after 20 min incubation time. As for [11C]CHO, kidney and liver were also the primary sites of uptake for [18F]dOC in vivo. Biodistribution data after simultaneous injection of both tracers into AR42J tumor bearing mice revealed slightly higher tumor uptake for [18F]dOC at 10 min post-injection, whereas [11C]CHO uptake was higher at later time points. In conclusion, [18F]dOC is taken up into AR42J rat pancreatic carcinoma and PC-3 human prostate cancer cells by a choline specific transport system. Similar transport rates of [18F]dOC and [11C]CHO result in comparable cellular uptake levels at early time points. In contrast to [18F]dOC, which is transported but not intracellularly trapped, the choline kinase substrate [11C]CHO is transported into tumor cells and retained. Thus, the signal obtained by imaging early after injection is mainly reflecting transport, whereas a valid quantification of choline kinase activity needs imaging at later time points. Further studies have to clarify whether quantification of the transport capacity or the choline kinase activity result in a better pathophysiological correlate and thus is the more useful process for tumor characterization.

Animals↗

PubMed2001

Optimisation of cyclotron production parameters for the 209Bi(alpha, 2n) 211At reaction related to biomedical use of 211At.

The cyclotron alpha beam production of 211At and of the contaminant 210At related to beam energy were studied. Radiochemical purification of 211At from the other main contaminant, 210Po, by an extraction procedure was also evaluated. To avoid impurities 28MeV has previously been considered as a maximum beam energy, but by using instead 29.1 MeV as a limit a large increase in EOB yield and sufficient radiochemical purity of extracted 211At were obtained. More cyclotrons could thereby deliver quantities useful for clinical cancer trials.

Astatine↗

PubMed1987