Top

Published in:

01-04-2012 | Original article

Sulfonylurea receptor as a target for molecular imaging of pancreas beta cells with ^99mTc-DTPA-glipizide

Authors: Chang-Sok Oh, Saady Kohanim, Fan-Lin Kong, Ho-Chun Song, Nathan Huynh, Richard Mendez, Mithu Chanda, E. Edmund Kim, David J. Yang

Published in: Annals of Nuclear Medicine | Issue 3/2012

Abstract

Objective

This study was aimed to assess pancreas beta cell activity using ^99mTc-diethyleneaminepentaacetic acid-glipizide (DTPA-GLP), a sulfonylurea receptor agent. The effect of DTPA-GLP on the blood glucose level in rats was also evaluated.

Methods

DTPA dianhydride was conjugated with GLP in the presence of sodium amide, yielding 60%. Biodistribution and planar images were obtained at 30–120 min after injection of ^99mTc-DTPA-GLP (1 mg/rat, 0.74 and 11.1 MBq per rat, respectively) in normal female Fischer 344 rats. The control group was given ^99mTc-DTPA. To demonstrate pancreas beta cell uptake of ^99mTc-DTPA-GLP via a receptor-mediated process, a group of rats was pretreated with streptozotocin (a beta cell toxin, 55 mg/kg, i.v.) and the images were acquired at immediately—65 min on day 5 post-treatment. The effect on the glucose levels after a single administration (ip) of DTPA-GLP was compared to glipizide (GLP) for up to 6 h.

Results

The structure of DTPA-GLP was confirmed by NMR, mass spectrometry and HPLC. Radiochemical purity assessed by ITLC was >96%. ^99mTc-DTPA-GLP showed increased pancreas-to-muscle ratios, whereas ^99mTc-DTPA showed decreased ratios at various time points. Pancreas could be visualized with ^99mTc-DTPA-GLP in normal rat, however, ^99mTc-DTPA has poor uptake suggesting the specificity of ^99mTc-DTPA-GLP. Pancreas beta cell uptake could be blocked by pre-treatment with streptozotocin. DTPA-GLP showed an equal or better response in lowering the glucose levels compared to the existing GLP drug.

Conclusions

It is feasible to use ^99mTc-DTPA-GLP to assess pancreas beta cell receptor recognition. ^99mTc-DTPA-GLP may be helpful in evaluating patients with diabetes, pancreatitis and pancreatic tumors.

Gepts W. Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes. 1965;14(10):619–33.PubMed

Meier JJ, Bhushan A, Butler AE, Rizza RA, Butler PC. Sustained beta cell apoptosis in patients with long-standing type 1 diabetes: indirect evidence for islet regeneration? Diabetologia. 2005;48(11):2221–8.PubMedCrossRef

Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003;52(1):102–10.PubMedCrossRef

Palmer JP, Fleming GA, Greenbaum CJ, Herold KC, Jansa LD, Kolb H, et al. C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function: report of an ADA workshop, 21–22 October 2001. Diabetes. 2004;53(1):250–64.PubMedCrossRef

Dwarakanathan A. Diabetes update. J Insur Med. 2006;38(1):20–30.PubMed

Robertson C, Drexler AJ, Vernillo AT. Update on diabetes diagnosis and management. J Am Dent Assoc. 2003;134 Spec No:16S–23S.

Polonsky KS, Given BD, Hirsch L, Shapiro ET, Tillil H, Beebe C, et al. Quantitative study of insulin secretion and clearance in normal and obese subjects. J Clin Investig. 1988;81(2):435–41.PubMedCrossRef

Kargar C, Ktorza A. Anatomical versus functional beta-cell mass in experimental diabetes. Diabetes Obes Metab. 2008;10(Suppl 4):43–53.PubMedCrossRef

Singhal T, Ding YS, Weinzimmer D, Normandin MD, Labaree D, Ropchan J, et al. Pancreatic beta cell mass PET imaging and quantification with [(11)C]DTBZ and [(18)F]FP-(+)-DTBZ in rodent models of diabetes. Mol Imaging Biol. 2011;13(5):973–84.PubMedCrossRef

10.

Aguilar-Bryan L, Clement JPt, Gonzalez G, Kunjilwar K, Babenko A, Bryan J. Toward understanding the assembly and structure of KATP channels. Physiol Rev. 1998;78(1):227–45.PubMed

11.

Proks P, Reimann F, Green N, Gribble F, Ashcroft F. Sulfonylurea stimulation of insulin secretion. Diabetes. 2002;51(Suppl 3):S368–76.PubMedCrossRef

12.

Schwanstecher M, Schwanstecher C, Dickel C, Chudziak F, Moshiri A, Panten U. Location of the sulphonylurea receptor at the cytoplasmic face of the beta-cell membrane. Br J Pharmacol. 1994;113(3):903–11.PubMed

13.

Pantalone KM, Kattan MW, Yu C, Wells BJ, Arrigain S, Jain A, Atreja A, Zimmerman RS. The risk of overall mortality in patients with type 2 diabetes receiving glipizide, glyburide, or glimepiride monotherapy: a retrospective analysis. Diabetes Care. 2010;33(6):1224–9.PubMedCrossRef

14.

Schneider S, Feilen PJ, Schreckenberger M, Schwanstecher M, Schwanstecher C, Buchholz HG, et al. In vitro and in vivo evaluation of novel glibenclamide derivatives as imaging agents for the non-invasive assessment of the pancreatic islet cell mass in animals and humans. Exp Clin Endocrinol Diabetes. 2005;113(7):388–95.PubMedCrossRef

15.

Schmitz A, Shiue CY, Feng Q, Shiue GG, Deng S, Pourdehnad MT, et al. Synthesis and evaluation of fluorine-18 labeled glyburide analogs as beta-cell imaging agents. Nucl Med Biol. 2004;31(4):483–91.PubMedCrossRef

16.

Schneider S, Ueberberg S, Korobeynikov A, Schechinger W, Schwanstecher C, Schwanstecher M, et al. Synthesis and evaluation of a glibenclamide glucose-conjugate: a potential new lead compound for substituted glibenclamide derivatives as islet imaging agents. Regul Pept. 2007;139(1–3):122–7.PubMedCrossRef

17.

Portha B, Tourrel-Cuzin C, Movassat J. Activation of the GLP-1 receptor signalling pathway: a relevant strategy to repair a deficient beta-cell mass. Exp Diabetes Res. 2011;2011:376509.PubMed

18.

Kitabchi AE, Kaminska E, Fisher JN, Sherman A, Pitts K, Bush A, et al. Comparative efficacy and potency of long-term therapy with glipizide or glyburide in patients with type 2 diabetes mellitus. Am J Med Sci. 2000;319(3):143–8.PubMedCrossRef

19.

Prendergast BD. Glyburide and glipizide, second-generation oral sulfonylurea hypoglycemic agents. Clin Pharm. 1984;3(5):473–85.PubMed

20.

Assadi M, Eftekhari M, Hozhabrosadati M, Saghari M, Ebrahimi A, Nabipour I, et al. Comparison of methods for determination of glomerular filtration rate: low and high-dose Tc-99m-DTPA renography, predicted creatinine clearance method, and plasma sample method. Int Urol Nephrol. 2008;40(4):1059–65.PubMedCrossRef

21.

Hui YH, Huang NH, Ebbert L, Bina H, Chiang A, Maples C, et al. Pharmacokinetic comparisons of tail-bleeding with cannula- or retro-orbital bleeding techniques in rats using six marketed drugs. J Pharmacol Toxicol Methods. 2007;56(2):256–64.PubMedCrossRef

22.

Wangler B, Beck C, Shiue CY, Schneider S, Schwanstecher C, Schwanstecher M, et al. Synthesis and in vitro evaluation of (S)-2-([11C]methoxy)-4-[3-methyl-1-(2-piperidine-1-yl-phenyl)-butyl-carbam oyl]-benzoic acid ([11C]methoxy-repaglinide): a potential beta-cell imaging agent. Bioorg Med Chem Lett. 2004;14(20):5205–9.PubMedCrossRef

23.

Wangler B, Schneider S, Thews O, Schirrmacher E, Comagic S, Feilen P, et al. Synthesis and evaluation of (S)-2-(2-[18F]fluoroethoxy)-4-([3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl-carbamoyl]-methyl)-benzoic acid ([18F]repaglinide): a promising radioligand for quantification of pancreatic beta-cell mass with positron emission tomography (PET). Nucl Med Biol. 2004;31(5):639–47.PubMedCrossRef

24.

Mishra AK, Hazari PP, Shukla G, Goel V, Chuttani K, Kumar N, et al. Synthesis of specific SPECT-radiopharmaceutical for tumor imaging based on methionine: (99m)Tc-DTPA-bis(methionine). Bioconjug Chem. 2010;21(2):229–39.PubMedCrossRef

25.

Mishra AK, Kakkar D, Tiwari AK, Chuttani K, Kaul A, Singh H. Comparative evaluation of glutamate-sensitive radiopharmaceuticals: technetium-99m-glutamic acid and technetium-99m-diethylenetriaminepentaacetic acid-bis(glutamate) conjugate for tumor imaging. Cancer Biother Radiopharm. 2010;25(6):645–55.PubMedCrossRef

26.

Hossain GA, Moinul Islam SM, Mahmood S, Khan N, Chakrabarty RK. Tc-99m DTPA scintigraphy in soft tissue tumor. Mymensingh Med J. 2005;14(2):185–8.PubMed

27.

Simpson NR, Souza F, Witkowski P, Maffei A, Raffo A, Herron A, et al. Visualizing pancreatic beta-cell mass with [11C]DTBZ. Nucl Med Biol. 2006;33(7):855–64.PubMedCrossRef

28.

Christ GJ, Day N, Santizo C, Sato Y, Zhao W, Sclafani T, Bakal R, Salman M, Davies K, Melman A. Intracorporal injection of hSlo cDNA restores erectile capacity in STZ-diabetic F-344 rats in vivo. Am J Physiol Heart Circ Physiol. 2004;287(4):H1544–53.PubMedCrossRef

29.

Goldstein R, Meyer T. Role of everolimus in pancreatic neuroendocrine tumors. Expert Rev Anticancer Ther. 2011;11(11):1653–65.PubMedCrossRef

30.

Snigur GL, Pisarev VB, Spasov AA, Samokhina MP, Bulanov AE. Mechanisms of toxic effect of streptozotocin on beta-cells in the islets of Langerhans. Bull Exp Biol Med. 2009;148(6):937–9.PubMedCrossRef

Title: Sulfonylurea receptor as a target for molecular imaging of pancreas beta cells with 99mTc-DTPA-glipizide
Authors: Chang-Sok Oh
Saady Kohanim
Fan-Lin Kong
Ho-Chun Song
Nathan Huynh
Richard Mendez
Mithu Chanda
E. Edmund Kim
David J. Yang
Publication date: 01-04-2012
Publisher: Springer Japan
Published in: Annals of Nuclear Medicine / Issue 3/2012
Print ISSN: 0914-7187
Electronic ISSN: 1864-6433
DOI: https://doi.org/10.1007/s12149-011-0569-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Sulfonylurea receptor as a target for molecular imaging of pancreas beta cells with ^99mTc-DTPA-glipizide

Abstract

Objective

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 3/2012

Acknowledgements to reviewers

Monte Carlo simulation of scintillation photons for the design of a high-resolution SPECT detector dedicated to human brain

Axillary lymph node accumulation on FDG-PET/CT after influenza vaccination

FDG-PET performed concurrently with initial I-131 ablation for differentiated thyroid cancer

Relation between FDG uptake and apparent diffusion coefficients in glioma and malignant lymphoma

Effective use of strontium-89 in osseous metastases