Pancreatic fate of a ¹²⁵I‐labelled mouse monoclonal antibody directed against pancreatic B‐cell surface ganglioside(s) in control and diabetic rats

Abstract

The possible use of a mouse monoclonal antibody directed against rat pancreatic B-cell surface ganglioside(s) and labelled with radioactive iodine for selective imaging of the endocrine pancreas by a non-invasive procedure was investigated by following its pancreatic fate in experiments conducted either in vitro by incubation of rat isolated pancreatic islets, acinar tissue and pancreatic pieces or in vivo after intravenous injection of the (125)I-labelled antibodies ([(125)I]gamma-G). Although the binding of [(125)I]gamma-G per microg protein was about one order of magnitude higher in isolated islets than in acinar tissue, no significant difference was detected when comparing pancreatic pieces or isolated islets from control animals and rats rendered diabetic by one or two prior administrations of streptozotocin (STZ rats). Likewise, except in one set of experiments, no significant difference was found between control animals and STZ rats, when measuring the radioactive content of the pancreatic gland, relative to that of plasma, 1-4 days after the intravenous injection of [(125)I]gamma-G. These findings indicate that under the present experimental conditions, the mouse monoclonal antibody labelled with radioactive iodine does not appear to be a promising tool for selective imaging of the endocrine pancreas, e.g. by single photon emission computerized tomography.

A genomic-based approach identifies FXYD domain containing ion transport regulator 2 (FXYD2)γa as a pancreatic beta cell-specific biomarker

“…Ideally, two basic criteria should be met for adequate beta cell imaging [6]: (1) beta cells should retain the tracer 100-to 1,000-fold more than the exocrine cells; and (2) agents that label beta cell surface proteins should do this at high enough concentrations to overcome imaging signals arising from unbound tracer retained in the extracellular and vascular spaces, and from tracer bound to the other tissues surrounding the pancreas. Agents being tested currently for BCM imaging include glibenclamide [6], glucagon-like peptide 1 receptor [7,8], sulfonylurea receptor [6], vesicular monoamine transporter 2 (VMAT2) [9][10][11][12][13] and gangliosides [14]. Unfortunately, the uptake/binding of these agents to beta cells, compared with exocrine pancreas and non-beta cells, is insufficient to allow reliable imaging of the BCM [6,15].…”

Visualizing pancreatic β-cell mass with [11C]DTBZ

“…Radioimmunoscintigraphy showed major differences in the pancreatic uptake of mAb between normal and diabetic rodents [10], but it was unclear if the method was suitable for in vivo imaging. Radioimmunoscintigraphy with antiganglioside mAbs has been less promising [13].…”

Longitudinal noninvasive PET-based cell mass estimates in a spontaneous diabetes rat model

“…It is unclear whether the method has clinical promise, as imaging was performed on pancreata ex vivo. Radioimmunoscintigraphy with anti-ganglioside mAbs has been less promising because of low specificity (19).…”