To synthesize ¹³¹I labeled anti-neuropilin-1 monoclonal antibody A6 (¹³¹I-A6) and evaluate its biodistribution and imaging in malignant glioma xenografts.

(1) A6 was labeled with ¹³¹I by Iodogen method under the optimum labeling conditions, then the labeling efficiency, radiochemical purity and stability were measured in vitro. (2) In vitro bioactivity, cellular uptake and receptor affinity of ¹³¹I-A6 with U87MG cells were measured. (3) The nude mice bearing human U87MG cells were randomly divided into 5 groups with 5 in each group. The nude mice were sacrificed by cervical dislocation and dissected at 24, 48, 72, 96, and 120 h, respectively, after intravenous injection of 1.2 MBq ¹³¹I-A6. The biodistribution of the agent was measured as %ID/g, and the ratios of tumor/blood (T/B) and tumor/muscle (T/M) were calculated. (4) SPECT/CT imaging was performed in 6 mice including 3 in the competitive inhibition control group at 24, 48, 72, 96, and 120 h post injection. Two-sample t test was used for data analysis.

(1) The labeling yield of ¹³¹I-A6 was (95.46±3.34)%, and the radiochemical purity was more than 95%. At 96 h of incubation in PBS, the radiochemical purity was more than 85%. (2) ¹³¹I-A6 had rapid accumulation in U87MG cells and reached the peak of (15.80±1.30)% at 1 h. When the probe was incubated with large excesses of non-radioactive A6, the uptake level of ¹³¹I-A6 in U87MG cells was significantly inhibited (t=2.862, P<0.05). K_d of ¹³¹I-A6 binding to NRP-1 was (1.67±0.14) nmol/L in U87MG cells. (3) Biodistribution study showed that the uptake in blood, liver and tumor was (8.00±1.42), (7.68±1.56) and (6.00±1.24) %ID/g at 24 h, respectively. The uptake in muscle, brain and bone was lower. The T/B and T/M were 0.78±0.10 and 3.20±0.30 at 24 h, and they reached the highest level of 1.87±0.50 and 7.13±0.24 at 120 h. (4) The SPECT imaging showed that the tumors could be visualized at 24 h and delineated more clearly at 120 h post injection of ¹³¹I-A6.

¹³¹I-A6 can be easily synthesized by Iodogen method with high radiochemical purity. The specific tumor uptake of ¹³¹I-A6, which correlates with NRP-1 expression in gliomas, suggests that it may be a new promising tumor targeting radiotracer.

Glioma; Neuropilin-1; Isotope labeling; Iodine radioisotopes; Radionuclide imaging; Mice, nude