In vivo biodistribution and pharmacokinetics of (18)F-labeled human C-peptide: evaluation in monkeys using positron emission tomography.
The recently observed beneficial effects exerted by C-peptide in insulin-dependent diabetes patients (IDDM) have instigated research into the mechanisms of C-peptide action as well as the location for it. Here we report in vivo biodistribution studies performed in monkeys using positron emission tomography (PET) and C-peptide labeled in the N-terminal with fluorine-18. Following iv injection of the radiotracer, dynamic decay data were collected over the chest and/or abdomens of the monkeys. The radioactivity distributed mainly to the kidneys, less to the heart and to some extent to the liver. Excretion of radioactivity into the urinary bladder was observed. Brain uptake was not detected in a static emission scan of the head performed at late times. Accumulation of radioactivity in the skeleton as a result of in vivo defluorination was not observed. Pharmacokinetic modeling of the regional concentrations of radioactivity over time resulted, for most organs, in two-compartment models. The organs with the highest radioactivity concentrations have been identified, enabling dose estimations for studies in humans with low or no C-peptide.
Karolinska Pharmacy, Karolinska Hospital and Institute, SE-171 76 Stockholm, Sweden. anna.fredriksson@ks.se
Anna
A
Fredriksson
Karin
K
Ekberg
Martin
M
Ingvar
Bo-Lennart
BL
Johansson
John
J
Wahren
Sharon
S
Stone-Elander
D000595:Amino Acid Sequence; D000818:Animals; D002096:C-Peptide / Q000493:pharmacokinetics*; D005260:Female; D005462:Fluorine Radioisotopes; D006207:Half-Life; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D008969:Molecular Sequence Data; D019275:Radiopharmaceuticals; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D002096:C-Peptide; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals