Novel [99mTcN]2+ labeled EGFR inhibitors as potential radiotracers for single photon emission computed tomography (SPECT) tumor imaging

Article abstract of DOI:10.3390/molecules19055508

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.