Preliminary study of ¹³¹I-Tyr-Nivolumab for PD-1-related theranostics of colon cancer

Objective: We synthesized theranostic agent ¹³¹I-Tyr-Nivolumab, which targets programmed cell death-1 (PD-1), and studied its preliminary application in the mouse model with orthotopic colon cancer and high PD-1 expression. Methods: ¹³¹I-Tyr-Nivolumab was prepared through indirect labeling, and the radiochemical purity and stability of products were evaluated. Ten mice with high expression of PD-l colon neoplasm in situ were randomly categorized into the treatment and untreated groups. In the treatment group, ¹³¹I-Tyr-Nivolumab (11.1 MBq/10 μg) was injected into the tail vein, and SPECT/CT was then performed to observe the distribution of the theranostic agent in mice at different time points (2, 4, 24, and 65 h) after injection. After 5 days of treatment, the expression of Bax and Bcl-2 proteins in tumor tissues were quantified by immunohistochemistry. Results: ¹³¹I-Tyr-Nivolumab had radiochemical purity greater than 99% and in vitro stability greater than 90% for 24 h. The theranostic agent was mainly distributed in the heart, liver, and intestinal tumors, and was eliminated by renal metabolism, and its uptake by the tumor tissue increased gradually at 2 h post-injection. The liver was visualized at 4 h post-injection, and the suspected tumor area of the intestine was clear at 24 h post-injection. Liver non-specific uptake was almost eliminated at 65 h post-injection. The ratios of radioactivity counts in the intestinal suspected tumor area to the whole-body radioactivity counts at 4, 24, and 65 h post-administration were (2.8 ± 0.3)%, (8.4 ± 0.2)%, and (1.8 ± 0.5)%, respectively. The treatment group had significantly higher expression rate of Bax protein [(22.23 ± 1.61)% vs. (13.64 ± 2.43)%, t = -5.476, P = 0.006] bur significantly lower expression rate of Bcl-2 protein [(13.81 ± 4.64)% vs. (25.57 ± 2.33)%, t = 3.902, P = 0.017] compared with the untreated group. Conclusion: ¹³1^I-Tyr-Nivolumab targeting PD-1 was successfully synthesized and can be used as a theranostic agent for SPECT imaging and internal irradiation therapy. This method could provide a new idea for the theranostics of colon cancer. (authors)