First-in-human application of 99mTc-CN7DG quantitative SPECT/CT in central nervous system tumors: a prospective comparison study with MRI and 18F-FDG PET/CT

To evaluate the novel SPECT tracer 99m Tc-CN7DG in a first-in-human clinical trial and assess its diagnostic value for central nervous system (CNS) tumors. Five Healthy volunteers were enrolled to assess the safety, biodistribution, and dosimetry of 99m Tc-CN7DG. Subsequently, we prospectively enrolled 20 patients suspected a CNS tumor underwent MR, 18 F-FDG PET/CT, and 99m Tc-CN7DG quantitative SPECT/CT. The number of lesions and semi-quantitative parameters including the SUVmax, SUVmean, SUVmin, and lesion-to-background ratio (LBR) were measured. No adverse reactions were observed in any volunteers or patients after the injection of 99m Tc-CN7DG. The mean whole-body effective dose estimated was 5.24 × 10⁻³ mSv/MBq. A total of 45 lesions were analyzed. Based on patient analysis, the detection rate was 90.0% (18/20) for 99m Tc-CN7DG and 45.0% (9/20) for 18 F-FDG. 99m Tc-CN7DG quantitative SPECT/CT demonstrated superior lesion detection to 18 F-FDG PET/CT (41 vs. 21, P < 0.0001), achieving a 44.4% reduction in the false-negative rate (sensitivity and accuracy: 0.911 vs. 0.467). Furthermore, it yielded significantly higher target-to-background contrast (LBRmax: 14.24 ± 9.44 vs. 1.15 ± 0.41; P < 0.0001). The Ki-67 index showed a correlation with both the lesional 18 F-FDG PET/CT SUVmax ( r = 0.72, P < 0.05) and LBRmax ( r = 0.71, P < 0.05). Based on lesion type analysis, 99m Tc-CN7DG demonstrated superior sensitivity for gliomas (5/5 patients, 8/8 lesions) and brain metastasis ( 99m Tc-CN7DG detecting 2 more patients and 10 more lesions than 18 F-FDG). In contrast, 18 F-FDG was the only tracer that successfully identified lymphoma cases (1/1 patient, 3/3 lesions). 99m Tc-CN7DG is a safe SPECT tracer and can serve as a complementary approach to conventional imaging when performed with quantitative SPECT/CT, especially for CNS tumor patients with false-negative 18 F-FDG results or contraindications to MRI.