Managed by Massimo Porta.
The zinc transporter 8 (ZnT8) has been suggested as a suitable target for non-invasive visualization of the functional pancreatic beta cell mass, due to both its pancreatic beta cell restricted expression and tight involvement in insulin secretion.
In order to examine the potential of ZnT8 as a surrogate target for beta cell mass, we performed mRNA transcription analysis in pancreatic compartments. A novel ZnT8 targeting antibody fragment Ab31 was radiolabeled with iodine-125, and evaluated by in vitro autoradiography in insulinoma and pancreas as well as by in vivo biodistribution. The evaluation was performed in a direct comparison with radio-iodinated Exendin-4.
Transcription of the ZnT8 mRNA was higher in islets of Langerhans compared to exocrine tissue. Ab31 targeted ZnT8 in the cytosol and on the plasma membrane with 108 nM affinity. Ab31 was successfully radiolabeled with iodine-125 with high yield and > 95% purity. [125I]Ab31 binding to insulinoma and pancreas was higher than for [125I]Exendin-4, but could only by partially competed away by 200 nM Ab31 in excess. The in vivo uptake of [125I]Ab31 was higher than [125I]Exendin-4 in most tissues, mainly due to slower clearance from blood.
We report a first-in-class ZnT8 imaging ligand for pancreatic imaging. Development with respect to ligand miniaturization and radionuclide selection is required for further progress. Transcription analysis indicates ZnT8 as a suitable target for visualization of the human endocrine pancreas.
Anonymous (2012) Sickle—a windowed adaptive trimming tool for FASTQ files using quality. https://github.com/najoshi/sickle. Accessed Nov 2013
Anonymous (2012) Picard. http://picard.sourceforge.net/. Accessed Nov 2013
RCoreTeam (2013) R: a language and environment for statistical computing. R Foundation for Statistical Computing. http://www.R-project.org/. Accessed Nov 2013
Gregory RW (2012) gplots: various R programming tools for plotting data. R package version 2.11.0. http://CRAN.R-project.org/package=gplots. Accessed Nov 2013
Béhé M, Gotthardt M, Behr TM (2006) Radioiodination of proteins and peptides. In: Celis JE (ed) Cell biology: a laboratory handbook, vol 1, 3rd edn. Elsevier Academic Press, New York, pp 149–154 CrossRef
Pietersz GA, Patrick MR, Chester KA (1998) Preclinical characterization and in vivo imaging studies of an engineered recombinant technetium-99 m-labeled metallothionein-containing anti-carcinoembryonic antigen single-chain antibody. J Nucl Med 39(1):47–56 PubMed
EST profile for SLC30A8 (Hs.532270). https://www.ncbi.nlm.nih.gov/UniGene/ESTProfileViewer.cgi?uglist=Hs.532270. Accessed 19 Aug 2017
Pimm MV, Gribben SJ (1994) Prevention of renal tubule re-absorption of radiometal (indium-111) labelled Fab fragment of a monoclonal antibody in mice by systemic administration of lysine. Eur J Nucl Meal 21:663–665 CrossRef
Jodal A, Lankat-Buttgereit B, Brom M, Schibli R, Béhé M (2014) A comparison of three (67/68)Ga-labelled Exendin-4 derivatives for β-cell imaging on the GLP-1 receptor: the influence of the conjugation site of NODAGA as chelator. EJNMMI Res 22(4):31 CrossRef
- Pancreatic imaging using an antibody fragment targeting the zinc transporter type 8: a direct comparison with radio-iodinated Exendin-4
Ram Kumar Selvaraju
Yann de Boysson
- Springer Milan
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