: Despite the contribution of changes in pancreatic
b-cell mass to the development of all forms of diabetes mellitus,
few robust approaches currently exist to monitor these
changes prospectively in vivo. Although magnetic-resonance
imaging (MRI) provides a potentially useful technique, targeting
MRI-active probes to the b cell has proved challenging.
Zinc ions are highly concentrated in the secretory granule,
but they are relatively less abundant in the exocrine
pancreas and in other tissues. We have therefore developed
functional dual-modal probes based on transition-metal chelates
capable of binding zinc. The first of these, Gd·1, binds
ZnII directly by means of an amidoquinoline moiety (AQA),
thus causing a large ratiometric Stokes shift in the fluorescence
from lem =410 to 500 nm with an increase in relaxivity
from r1=4.2 up to 4.9 mm1 s
1
. The probe is efficiently accumulated
into secretory granules in b-cell-derived lines and
isolated islets, but more poorly by non-endocrine cells, and
leads to a reduction in T1 in human islets. In vivo murine
studies of Gd·1 have shown accumulation of the probe in
the pancreas with increased signal intensity over 140 minutes.