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

Sweet, Ian R; Cook, Daniel L; Lernmark, Åke LU ; Greenbaum, Carla J and Krohn, Kenneth A (2004) In Diabetes Technology & Therapeutics 6(5). p.652-659
Abstract
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... (More)
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. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes Technology & Therapeutics
volume
6
issue
5
pages
652 - 659
publisher
Mary Ann Liebert, Inc.
external identifiers
  • scopus:6044234743
ISSN
1520-9156
DOI
10.1089/dia.2004.6.652
language
English
LU publication?
no
id
ad7eb6ce-3519-4eb7-a951-68832f6933bc (old id 1129982)
date added to LUP
2008-06-18 14:42:02
date last changed
2017-12-10 03:51:02
@article{ad7eb6ce-3519-4eb7-a951-68832f6933bc,
  abstract     = {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.},
  author       = {Sweet, Ian R and Cook, Daniel L and Lernmark, Åke and Greenbaum, Carla J and Krohn, Kenneth A},
  issn         = {1520-9156},
  language     = {eng},
  number       = {5},
  pages        = {652--659},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Diabetes Technology & Therapeutics},
  title        = {Non-invasive imaging of beta cell mass: a quantitative analysis.},
  url          = {http://dx.doi.org/10.1089/dia.2004.6.652},
  volume       = {6},
  year         = {2004},
}