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Background: Epidermal growth factor receptor (EGFR) overexpressed in colorectal cancer (CRC) is a tumor target for developing the anti-tumor theranostic agents. Cetuximab, an anti-EGFR monoclonal antibody against EGFR-positive tumors, inhibits cell proliferation and growth was labeled with radioactive 111 indium ( 111 In) in this study for diagnosing EGFR-positive CRC. The aim of this study was to evaluate the efficacy of noninvasive nuclear imaging agent 111 In-cetuximab and investigate the biological distribution of 111 In-cetuximab in the HCT-15-induced EGFR-positive CRC tumor xenografts., Methods: We conjugated cetuximab with an isotope chelator, diethylene triamine penta acetic acid (DTPA), and consequently labeled cetuximab-DTPA with 111 In and measured the labeling efficacy by an instant thin layer chromatography (iTLC). Furthermore, the 111 In-cetuximab was investigated and compared for imaging small (50 mm 3 ) and large (250 mm 3 ) tumor of CRC xenografts, respectively., Results: The conjugated ratio between cetuximab and DTPA was 1:6 measured by MALDI-TOF-MS. The better labeling concentration of cetuximab with 10 mCi of 111 In was calculated and experimented as 48 μg, resulting in labeling efficacy >80% detected by iTLC. The results revealed that the 111 In-cetuximab accumulated in the both sizes of tumors as a reliable noninvasive diagnostic agent, whereas the ratio of tumor to muscle in the large tumor was 7.5-fold. The biodistribution data indicated that the 111 In-cetuximab bound to tumor specifically that was higher than that in other organs., Conclusion: We suggested that the 111 In-cetuximab was potential for early diagnosis and prognostic monitor of EGFR-positive CRC in further clinical practice., (Copyright © 2017. Published by Elsevier Taiwan LLC.)

A non-invasive method of pancreatic β-cell mass measurement is needed to enhance our understanding of the pathogenesis of diabetes, facilitate the early diagnosis of this disease, and promote the development of novel therapeutics. Here, we described the synthesis of a novel indium-111 ( 111 In) exendin-4 derivative, [Lys 12 (In-BnDTPA-Ahx)]exendin-4, through a process involving isothiocyanate-benzyl-DTPA (BnDTPA) and 6-aminohexanoic acid (Ahx) attached to an ɛ-amino group at the lysine-12 residue. We further evaluated the potential use of this derivative as a SPECT probe for pancreatic β-cell imaging. An in vitro binding assay revealed that [Lys 12 ( nat In-BnDTPA-Ahx)]exendin-4 has a high affinity for GLP-1 receptors (IC 50 =0.43nM). In biodistribution experiments involving normal mice, high [Lys 12 ( 111 In-BnDTPA-Ahx)]exendin-4 uptake was observed in the pancreas (21.8 ± 4.0%ID/g) and was maintained for 2h after injection. Pre-injection of excess exendin(9-39) markedly reduced the pancreatic uptake of [Lys 12 ( 111 In-BnDTPA-Ahx)]exendin-4 (95.2%), indicating that the uptake of this tracer is specific and mediated by GLP-1 receptors. Ex vivo autoradiography experiments involving pancreatic sections from MIP-GFP mice confirmed the accumulation of [Lys 12 ( 111 In-BnDTPA-Ahx)]exendin-4 in pancreatic β-cells. Finally, in mice, [Lys 12 ( 111 In-BnDTPA-Ahx)]exendin-4 SPECT/CT yielded clear images of the pancreas at 30min post-injection. In conclusion, SPECT with [Lys 12 ( 111 In-BnDTPA-Ahx)]exendin-4 enables to visualize β-cells in vivo non-invasively., (Copyright © 2017 Elsevier Ltd. All rights reserved.)