Non-invasive imaging of beta cell mass: a quantitative analysis.

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Non-invasive imaging of beta cell mass: a quantitative analysis. / Sweet, Ian R; Cook, Daniel L; Lernmark, Åke; Greenbaum, Carla J; Krohn, Kenneth A.

In: Diabetes Technology & Therapeutics, Vol. 6, No. 5, 2004, p. 652-659.

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Sweet, Ian R ; Cook, Daniel L ; Lernmark, Åke ; Greenbaum, Carla J ; Krohn, Kenneth A. / Non-invasive imaging of beta cell mass: a quantitative analysis. In: Diabetes Technology & Therapeutics. 2004 ; Vol. 6, No. 5. pp. 652-659.

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TY - JOUR

T1 - Non-invasive imaging of beta cell mass: a quantitative analysis.

AU - Sweet, Ian R

AU - Cook, Daniel L

AU - Lernmark, Åke

AU - Greenbaum, Carla J

AU - Krohn, Kenneth A

PY - 2004

Y1 - 2004

N2 - BACKGROUND: Currently there are major efforts to develop strategies for the in vivo imaging of pancreatic beta cell mass as a clinical and investigational tool for detecting and tracking the loss of beta cells that underlies the progression of Type I diabetes. However, beta cells constitute only about 1% of pancreatic mass and are distributed throughout the pancreas within tiny islets of Langerhans that are each less than the spatial resolution of non-invasive imaging technologies. METHODS: To estimate the requisite binding characteristics of a candidate beta cell imaging agent, calculations of the beta cell contribution to a positron emission tomography signal were made using simple equations. These were based on the relative population of beta cells and non-beta cells within the pancreas and surrounding tissue and an equation describing equilibrium ligand binding. RESULTS: The calculations show that two criteria must be met: (1) The low-volume fraction of beta cells within the exocrine pancreas (about 1:100) requires that beta cells retain labeled imaging agents at least 1,000-fold more strongly than exocrine cells. (2) Agents that label cell surface receptors, even if beta cell-specific, must do so at a high enough level so that the imaging signal arising from unbound label retained in extracellular spaces must not overwhelm signals from labeled beta cells. CONCLUSIONS: The limits developed here can serve as criteria for identifying candidate imaging agents for the in vivo imaging of beta cell mass, thereby avoiding expensive preclinical development using compounds that have no chance of success.

AB - BACKGROUND: Currently there are major efforts to develop strategies for the in vivo imaging of pancreatic beta cell mass as a clinical and investigational tool for detecting and tracking the loss of beta cells that underlies the progression of Type I diabetes. However, beta cells constitute only about 1% of pancreatic mass and are distributed throughout the pancreas within tiny islets of Langerhans that are each less than the spatial resolution of non-invasive imaging technologies. METHODS: To estimate the requisite binding characteristics of a candidate beta cell imaging agent, calculations of the beta cell contribution to a positron emission tomography signal were made using simple equations. These were based on the relative population of beta cells and non-beta cells within the pancreas and surrounding tissue and an equation describing equilibrium ligand binding. RESULTS: The calculations show that two criteria must be met: (1) The low-volume fraction of beta cells within the exocrine pancreas (about 1:100) requires that beta cells retain labeled imaging agents at least 1,000-fold more strongly than exocrine cells. (2) Agents that label cell surface receptors, even if beta cell-specific, must do so at a high enough level so that the imaging signal arising from unbound label retained in extracellular spaces must not overwhelm signals from labeled beta cells. CONCLUSIONS: The limits developed here can serve as criteria for identifying candidate imaging agents for the in vivo imaging of beta cell mass, thereby avoiding expensive preclinical development using compounds that have no chance of success.

U2 - 10.1089/dia.2004.6.652

DO - 10.1089/dia.2004.6.652

M3 - Article

VL - 6

SP - 652

EP - 659

JO - Diabetes Technology and Therapeutics

JF - Diabetes Technology and Therapeutics

SN - 1520-9156

IS - 5

ER -