Skip to main content
Top
Published in: Diabetologia 12/2018

01-12-2018 | Commentary

Futility of attempts to detect and quantify beta cells by PET imaging in the pancreas: why it is time to abandon the approach

Authors: Abass Alavi, Thomas J. Werner

Published in: Diabetologia | Issue 12/2018

Login to get access

Abstract

In this commentary, we describe the limitations of positron emission tomography (PET) in visualising and characterising beta cell mass in the native pancreas in healthy individuals and those diagnosed with diabetes. Imaging with PET requires a large mass of targeted cells or other structures in the range of approximately 8–10 cm3. Since islets occupy only 1% of the pancreatic volume and are dispersed throughout the organ, it is our view that uptake of PET tracers, including [18F]fluoropropyl-(+)-dihydrotetrabenazine, in islets cannot be successfully detected by current imaging modalities. Therefore, we dispute the feasibility of PET imaging for the detection of loss of beta cells in the native pancreas in individuals with diabetes. However, we believe this novel approach can be successfully employed to visualise beta cell mass in individuals with hyperinsulinism and transplanted islets.
Literature
1.
go back to reference Hickeson M, Yun M, Matthies A et al (2002) Use of a corrected standardized uptake value based on the lesion size on CT permits accurate characterization of lung nodules on FDG-PET. Eur J Nucl Med Mol Imaging 29:1639–1647CrossRef Hickeson M, Yun M, Matthies A et al (2002) Use of a corrected standardized uptake value based on the lesion size on CT permits accurate characterization of lung nodules on FDG-PET. Eur J Nucl Med Mol Imaging 29:1639–1647CrossRef
2.
go back to reference Rousset O, Rahmim A, Alavi A, Zaidi H (2007) Partial volume correction strategies in PET. PET Clin 2:235–249CrossRef Rousset O, Rahmim A, Alavi A, Zaidi H (2007) Partial volume correction strategies in PET. PET Clin 2:235–249CrossRef
3.
go back to reference Soret M, Bacharach SL, Buvat I (2007) Partial-volume effect in PET tumor imaging. J Nucl Med: official publication, Society of Nuclear Medicine 48:932–945CrossRef Soret M, Bacharach SL, Buvat I (2007) Partial-volume effect in PET tumor imaging. J Nucl Med: official publication, Society of Nuclear Medicine 48:932–945CrossRef
4.
go back to reference Lubberink M, Schneider H, Bergstrom M, Lundqvist H (2002) Quantitative imaging and correction for cascade gamma radiation of 76Br with 2D and 3D PET. Phys Med Biol 47:3519–3534CrossRef Lubberink M, Schneider H, Bergstrom M, Lundqvist H (2002) Quantitative imaging and correction for cascade gamma radiation of 76Br with 2D and 3D PET. Phys Med Biol 47:3519–3534CrossRef
5.
go back to reference Cheng G, Werner TJ, Newberg A, Alavi A (2016) Failed PET application attempts in the past, can we avoid them in the future? Mol Imaging Biol 18:797–802CrossRef Cheng G, Werner TJ, Newberg A, Alavi A (2016) Failed PET application attempts in the past, can we avoid them in the future? Mol Imaging Biol 18:797–802CrossRef
6.
go back to reference Alavi A, Werner TJ, Hoilund-Carlsen PF (2017) What can be and what cannot be accomplished with PET: rectifying ongoing misconceptions. Clin Nucl Med 42:603–605CrossRef Alavi A, Werner TJ, Hoilund-Carlsen PF (2017) What can be and what cannot be accomplished with PET: rectifying ongoing misconceptions. Clin Nucl Med 42:603–605CrossRef
8.
go back to reference Barrio JR (2018) The irony of PET tau probe specificity. J Nucl Med 59:115–116CrossRef Barrio JR (2018) The irony of PET tau probe specificity. J Nucl Med 59:115–116CrossRef
9.
go back to reference Joshi NV, Vesey AT, Williams MC et al (2014) 18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial. Lancet 383:705–713CrossRef Joshi NV, Vesey AT, Williams MC et al (2014) 18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial. Lancet 383:705–713CrossRef
10.
go back to reference Goland R, Freeby M, Parsey R et al (2009) 11C-dihydrotetrabenazine PET of the pancreas in subjects with long-standing type 1 diabetes and in healthy controls. J Nucl Med 50:382–389CrossRef Goland R, Freeby M, Parsey R et al (2009) 11C-dihydrotetrabenazine PET of the pancreas in subjects with long-standing type 1 diabetes and in healthy controls. J Nucl Med 50:382–389CrossRef
11.
go back to reference Singhal T, Ding YS, Weinzimmer D et al (2011) Pancreatic beta cell mass PET imaging and quantification with [11C]DTBZ and [18F]FP-(+)-DTBZ in rodent models of diabetes. Mol Imaging Biol 13:973–984CrossRef Singhal T, Ding YS, Weinzimmer D et al (2011) Pancreatic beta cell mass PET imaging and quantification with [11C]DTBZ and [18F]FP-(+)-DTBZ in rodent models of diabetes. Mol Imaging Biol 13:973–984CrossRef
12.
go back to reference Cline GW, Zhao X, Jakowski AB, Soeller WC, Treadway JL (2011) Islet-selectivity of G-protein coupled receptor ligands evaluated for PET imaging of pancreatic beta-cell mass. Biochem Biophys Res Commun 412:413–418CrossRef Cline GW, Zhao X, Jakowski AB, Soeller WC, Treadway JL (2011) Islet-selectivity of G-protein coupled receptor ligands evaluated for PET imaging of pancreatic beta-cell mass. Biochem Biophys Res Commun 412:413–418CrossRef
13.
go back to reference Ichise M, Harris PE (2010) Imaging of beta-cell mass and function. J Nucl Med 51:1001–1004CrossRef Ichise M, Harris PE (2010) Imaging of beta-cell mass and function. J Nucl Med 51:1001–1004CrossRef
14.
go back to reference Kung MP, Hou C, Lieberman BP et al (2008) In vivo imaging of beta-cell mass in rats using 18F-FP-(+)-DTBZ: a potential PET ligand for studying diabetes mellitus. J Nucl Med 49:1171–1176CrossRef Kung MP, Hou C, Lieberman BP et al (2008) In vivo imaging of beta-cell mass in rats using 18F-FP-(+)-DTBZ: a potential PET ligand for studying diabetes mellitus. J Nucl Med 49:1171–1176CrossRef
15.
go back to reference Souza F, Simpson N, Raffo A et al (2006) Longitudinal noninvasive PET-based beta cell mass estimates in a spontaneous diabetes rat model. J Clin Invest 116:1506–1513CrossRef Souza F, Simpson N, Raffo A et al (2006) Longitudinal noninvasive PET-based beta cell mass estimates in a spontaneous diabetes rat model. J Clin Invest 116:1506–1513CrossRef
16.
go back to reference Blomberg BA, Codreanu I, Cheng G, Werner TJ, Alavi A (2013) Beta-cell imaging: call for evidence-based and scientific approach. Mol Imaging Biol 15:123–130CrossRef Blomberg BA, Codreanu I, Cheng G, Werner TJ, Alavi A (2013) Beta-cell imaging: call for evidence-based and scientific approach. Mol Imaging Biol 15:123–130CrossRef
17.
go back to reference Fagerholm V, Mikkola KK, Ishizu T et al (2010) Assessment of islet specificity of dihydrotetrabenazine radiotracer binding in rat pancreas and human pancreas. J Nucl Med 51:1439–1446CrossRef Fagerholm V, Mikkola KK, Ishizu T et al (2010) Assessment of islet specificity of dihydrotetrabenazine radiotracer binding in rat pancreas and human pancreas. J Nucl Med 51:1439–1446CrossRef
18.
go back to reference Salavati A, Borofsky S, Boon-Keng TK et al (2015) Application of partial volume effect correction and 4D PET in the quantification of FDG avid lung lesions. Mol Imaging Biol 17:140–148CrossRef Salavati A, Borofsky S, Boon-Keng TK et al (2015) Application of partial volume effect correction and 4D PET in the quantification of FDG avid lung lesions. Mol Imaging Biol 17:140–148CrossRef
20.
go back to reference Sweet IR, Cook DL, Lernmark A, Greenbaum CJ, Krohn KA (2004) Non-invasive imaging of beta cell mass: a quantitative analysis. Diabetes Technol Ther 6:652–659CrossRef Sweet IR, Cook DL, Lernmark A, Greenbaum CJ, Krohn KA (2004) Non-invasive imaging of beta cell mass: a quantitative analysis. Diabetes Technol Ther 6:652–659CrossRef
21.
go back to reference Arifin DR, Bulte JW (2011) Imaging of pancreatic islet cells. Diabetes Metab Res Rev 27:761–766CrossRef Arifin DR, Bulte JW (2011) Imaging of pancreatic islet cells. Diabetes Metab Res Rev 27:761–766CrossRef
22.
go back to reference Kung HF, Lieberman BP, Zhuang ZP et al (2008) In vivo imaging of vesicular monoamine transporter 2 in pancreas using an (18)F epoxide derivative of tetrabenazine. Nucl Med Biol 35:825–837CrossRef Kung HF, Lieberman BP, Zhuang ZP et al (2008) In vivo imaging of vesicular monoamine transporter 2 in pancreas using an (18)F epoxide derivative of tetrabenazine. Nucl Med Biol 35:825–837CrossRef
23.
go back to reference Harris PE, Leibel RL (2012) Neurofunctional imaging of beta-cell dynamics. Diabetes Obes Metab 14(Suppl 3):91–100CrossRef Harris PE, Leibel RL (2012) Neurofunctional imaging of beta-cell dynamics. Diabetes Obes Metab 14(Suppl 3):91–100CrossRef
24.
go back to reference Harris PE, Farwell MD, Ichise M (2013) PET quantification of pancreatic VMAT 2 binding using (+) and (-) enantiomers of [(1)(8)F]FP-DTBZ in baboons. Nucl Med Biol 40:60–64CrossRef Harris PE, Farwell MD, Ichise M (2013) PET quantification of pancreatic VMAT 2 binding using (+) and (-) enantiomers of [(1)(8)F]FP-DTBZ in baboons. Nucl Med Biol 40:60–64CrossRef
25.
go back to reference Naganawa M, Lin SF, Lim K et al (2016) Evaluation of pancreatic VMAT2 binding with active and inactive enantiomers of (18)F-FP-DTBZ in baboons. Nucl Med Biol 43:743–751CrossRef Naganawa M, Lin SF, Lim K et al (2016) Evaluation of pancreatic VMAT2 binding with active and inactive enantiomers of (18)F-FP-DTBZ in baboons. Nucl Med Biol 43:743–751CrossRef
27.
go back to reference Blomberg BA, Moghbel MC, Alavi A (2012) PET imaging of beta-cell mass: is it feasible? Diabetes Metab Res Rev 28:601–602CrossRef Blomberg BA, Moghbel MC, Alavi A (2012) PET imaging of beta-cell mass: is it feasible? Diabetes Metab Res Rev 28:601–602CrossRef
28.
go back to reference Kwee TC, Basu S, Saboury B, Torigian DA, Naji A, Alavi A (2011) Beta-cell imaging: opportunities and limitations. J Nucl Med 52:493CrossRef Kwee TC, Basu S, Saboury B, Torigian DA, Naji A, Alavi A (2011) Beta-cell imaging: opportunities and limitations. J Nucl Med 52:493CrossRef
29.
go back to reference Eriksson O, Jahan M, Johnstrom P et al (2010) In vivo and in vitro characterization of [18F]-FE-(+)-DTBZ as a tracer for beta-cell mass. Nucl Med Biol 37:357–363CrossRef Eriksson O, Jahan M, Johnstrom P et al (2010) In vivo and in vitro characterization of [18F]-FE-(+)-DTBZ as a tracer for beta-cell mass. Nucl Med Biol 37:357–363CrossRef
30.
go back to reference Eriksson O, Laughlin M, Brom M et al (2016) In vivo imaging of beta cells with radiotracers: state of the art, prospects and recommendations for development and use. Diabetologia 59:1340–1349CrossRef Eriksson O, Laughlin M, Brom M et al (2016) In vivo imaging of beta cells with radiotracers: state of the art, prospects and recommendations for development and use. Diabetologia 59:1340–1349CrossRef
31.
go back to reference Eriksson O, Mintz A, Liu C, Yu M, Naji A, Alavi A (2014) On the use of [18F]DOPA as an imaging biomarker for transplanted islet mass. Ann Nucl Med 28:47–52CrossRef Eriksson O, Mintz A, Liu C, Yu M, Naji A, Alavi A (2014) On the use of [18F]DOPA as an imaging biomarker for transplanted islet mass. Ann Nucl Med 28:47–52CrossRef
32.
go back to reference Meintjes M, Endozo R, Dickson J et al (2013) 18F-DOPA PET and enhanced CT imaging for congenital hyperinsulinism: initial UK experience from a technologist's perspective. Nucl Med Commun 34:601–608CrossRef Meintjes M, Endozo R, Dickson J et al (2013) 18F-DOPA PET and enhanced CT imaging for congenital hyperinsulinism: initial UK experience from a technologist's perspective. Nucl Med Commun 34:601–608CrossRef
Metadata
Title
Futility of attempts to detect and quantify beta cells by PET imaging in the pancreas: why it is time to abandon the approach
Authors
Abass Alavi
Thomas J. Werner
Publication date
01-12-2018
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 12/2018
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-018-4676-1

Other articles of this Issue 12/2018

Diabetologia 12/2018 Go to the issue

Up Front

Up Front