In vivo imaging of beta-cell mass in rats using 18F-FP-(+)-DTBZ: a potential PET ligand for studying diabetes mellitus.
Recent studies on gene expression of beta-cell mass (BCM) in the pancreas showed that vesicular monoamine transporter 2 (VMAT2) is highly expressed in the BCM (mainly in the islets of Langerhans). Imaging pancreatic BCM may provide an important tool for understanding the relationship between loss of insulin-secreting beta-cells and onset of diabetes mellitus. In this article, 9-fluoropropyl-(+)-dihydrotetrabenazine (FP-(+)-DTBZ), which is a VMAT2 imaging agent, was evaluated as a PET agent for estimating BCM in vivo.


METHODS
Organ biodistribution after an intravenous injection of (18)F-FP-(+)-DTBZ (active isomer) and (18)F-FP-(-)-DTBZ (inactive isomer) was evaluated in normal rats. The specificity of uptake of (18)F-FP-(+)-DTBZ was assessed by a pretreatment (3.8 mg of (+)-DTBZ per kilogram and 3.5 mg of FP-(+)-DTBZ per kilogram, intravenously, 5 min prior) or coadministration (2 mg of (+)-DTBZ per kilogram). PET studies were performed in normal rats.


RESULTS
The in vivo biodistribution of (18)F-FP-(+)-DTBZ in rats showed the highest uptake in the pancreas (5% dose/g at 30 min after injection), whereas (18)F-FP-(-)-DTBZ showed a very low pancreas uptake. Rats pretreated with FP-(+)-DTBZ displayed a 78% blockade of pancreas uptake. PET studies in normal rats demonstrated an avid pancreas uptake of (18)F-FP-(+)-DTBZ.


CONCLUSIONS
The preliminary data obtained with (18)F-FP-(+)-DTBZ suggest that this fluorinated derivative of DTBZ shows good pancreas specificity and has the potential to be useful for quantitative measurement of VMAT2 binding sites reflecting BCM in the pancreas.
Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Mei-Ping
MP
Kung
Catherine
C
Hou
Brian P
BP
Lieberman
Shunichi
S
Oya
Datta E
DE
Ponde
Eric
E
Blankemeyer
Daniel
D
Skovronsky
Michael R
MR
Kilbourn
Hank F
HF
Kung
D000818:Animals; D003920:Diabetes Mellitus / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D050493:Vesicular Monoamine Transport Proteins; C032811:dihydrotetrabenazine; D013747:Tetrabenazine