Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with 68Ga-DOTA-octreotide: a potential PET tracer for beta cell mass measurement.
Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, and the loss or dysfunction of pancreatic beta cells has been reported before the appearance of clinical symptoms and hyperglycemia. To evaluate beta cell mass (BCM) for improving the detection and treatment of DM at earlier stages, we focused on somatostatin receptors that are highly expressed in the pancreatic beta cells, and developed a positron emission tomography (PET) probe derived from octreotide, a metabolically stable somatostatin analog. Octreotide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a chelating agent, and labeled with (68)Gallium ((68)Ga). After intravenous injection of (68)Ga-DOTA-octreotide, a 90-min emission scan of the abdomen was performed in normal and DM model rats. The PET studies showed that (68)Ga-DOTA-octreotide radioactivity was highly accumulated in the pancreas of normal rats and that the pancreatic accumulation was significantly reduced in the rats administered with an excess amount of unlabeled octreotide or after treatment with streptozotocin, which was used for the chemical induction of DM in rats. These results were in good agreement with the ex vivo biodistribution data. These results indicated that the pancreatic accumulation of (68)Ga-DOTA-octreotide represented specific binding to the somatostatin receptors and reflected BCM. Therefore, PET imaging with (68)Ga-DOTA-octreotide could be a potential tool for evaluating BCM.
Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan; Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan; Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
Takeo
T
Sako
Koki
K
Hasegawa
Mie
M
Nishimura
Yousuke
Y
Kanayama
Yasuhiro
Y
Wada
Emi
E
Hayashinaka
Yilong
Y
Cui
Yosky
Y
Kataoka
Michio
M
Senda
Yasuyoshi
Y
Watanabe
D000818:Animals; D002452:Cell Count / Q000379:methods*; D003920:Diabetes Mellitus / Q000473:pathology*; D005710:Gallium Radioisotopes / Q000032:analysis / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000473:pathology*; D008297:Male; D015282:Octreotide / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D009942:Organometallic Compounds / Q000032:analysis* / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000473:pathology*; D049268:Positron-Emission Tomography / Q000379:methods*; D011849:Radioactive Tracers; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000032:analysis*
C587879:68Ga-DOTA-octreotide; D005710:Gallium Radioisotopes; D009942:Organometallic Compounds; D011849:Radioactive Tracers; D017481:Receptors, Somatostatin; D015282:Octreotide
(68)Ga-DOTA-octreotide; AC; BCM; DOTA-OC; DTBZ; Diabetes mellitus; FBP; FORE; Fourier rebinning; GLP-1; ID; MAP; Pancreatic beta cell mass; Positron emission tomography; SSTR; STZ; Somatostatin receptor; VOI; adenylyl cyclase; beta cell mass; dihydrotetrabenazine; filtered back-projection; glucagon-like peptide-1; injected dose; maximum a posteriori; somatostatin receptor; streptozotocin; volumetric region of interest