In Vivo Imaging of GLP-1R with a Targeted Bimodal
PET/Fluorescence Imaging Agent
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Abstract
Accurate visualization and quantification
of β-cell mass
is critical for the improved understanding, diagnosis, and treatment
of both type 1 diabetes (T1D) and insulinoma. Here, we describe the
synthesis of a bimodal imaging probe (PET/fluorescence) for imaging
GLP-1R expression in the pancreas and in pancreatic islet cell tumors.
The conjugation of a bimodal imaging tag containing a near-infrared
fluorescent dye, and the copper chelator sarcophagine to the GLP-1R
targeting peptide exendin-4 provided the basis for the bimodal imaging
probe. Conjugation was performed via a novel sequential one-pot synthetic
procedure including <sup>64</sup>Cu radiolabeling and copper-catalyzed
click-conjugation. The bimodal imaging agent <sup>64</sup>Cu-E4-Fl
was synthesized in good radiochemical yield and specific activity
(RCY = 36%, specific activity: 141 μCi/μg, >98% radiochemical
purity). The agent showed good performance in vivo and ex vivo, visualizing
small xenografts (<2 mm) with PET and pancreatic β-cell mass
by phosphor autoradiography. Using the fluorescent properties of the
probe, we were able to detect individual pancreatic islets, confirming
specific binding to GLP-1R and surpassing the sensitivity of the radioactive
label. The use of bimodal PET/fluorescent imaging probes is promising
for preoperative imaging and fluorescence-assisted analysis of patient
tissues. We believe that our procedure could become relevant as a
protocol for the development of bimodal imaging agents