Abstract: The epidermal growth factor receptor (EGFR) is overexpressed in many cancers, including breast, ovarian, endometrial and non-small cell lung cancer. An EGFR-specific imaging agent could facilitate clinical evaluation of primary tumors or metastases. To achieve this goal, 4-(2-aminoethylamino)-6,7-dimethoxyquinazoline (ADMQ) was synthesized based on a 4-aminoquinazoline core and then conjugated with N-mercapto- acetylglycine (MAG) and N-mercaptoacetyltriglycine (MAG3), respectively, to give compounds 1 and 2. The final complexes [99mTcN]-1 and [99mTcN]-2 were successfully obtained with radiochemical purities of >99% and >98% as measured by radio-HPLC. No decomposition of the two complexes at room temperature was observed over a period of 2 h. Their partition coefficients indicated they were hydrophilic and the electrophoresis results showed they were negatively charged. Biodistribution in tumor-bearing mice demonstrated that the two new complexes showed tumor accumulation, high tumor-tomuscle (T/M) ratios and fast clearance from blood and muscle. Between the two compounds, the 99mTcN-MAG3-ADMQ ([99mTcN]-2) showed the better characteristics, with the tumor/muscle and tumor/blood ratios reached 2.11 and 1.90 at 60 min post-injection, 4.20 and 1.10 at 120 min post-injection, suggesting it could be a promising radiotracer for SPECT tumor imaging.
Keywords: [99mTcN]2+ complex; 4-aminoquinazoline; EGFR; tumor imaging
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Zhao, M.; Ning, H.; Feng, M.; Li, S.; Chang, J.; Qi, C. Novel [99mTcN]2+ Labeled EGFR Inhibitors as Potential Radiotracers for Single Photon Emission Computed Tomography (SPECT) Tumor Imaging. Molecules 2014, 19, 5508-5521.
Zhao M, Ning H, Feng M, Li S, Chang J, Qi C. Novel [99mTcN]2+ Labeled EGFR Inhibitors as Potential Radiotracers for Single Photon Emission Computed Tomography (SPECT) Tumor Imaging. Molecules. 2014; 19(5):5508-5521.
Zhao, Mingxia; Ning, Hongyu; Feng, Man; Li, Shilei; Chang, Jin; Qi, Chuanmin. 2014. "Novel [99mTcN]2+ Labeled EGFR Inhibitors as Potential Radiotracers for Single Photon Emission Computed Tomography (SPECT) Tumor Imaging." Molecules 19, no. 5: 5508-5521.