Developing P-glycoprotein inhibitor marked by PET

Objective To explore a PET probe, ¹¹C-GF120918 in the assessing of the function and significance of P-glycoprotein(P-gp) and breast cancer resistance protein(BCRP).

Methods The mice were injected with chemically synthesized ¹¹C-GF120918. An automatic gamma counter was used to measure the ¹¹C-GF120918 radiation intensity of the various organs of the mice at different times and dosages. Simultaneously, HPLC was employed to detect the metabolism of ¹¹C-GF120918 in the brain and blood of the mice. The four mice groups, namely, P-gp knockdown mice, BCRP knockdown mice, P-gp/BCRP knockdown mice, and wild mice, were manually injected with ¹¹C-GF120918. The radiation intensity of ¹¹C-GF120918 in the mice brain was detected by PET.

Results After the ¹¹C-GF120918 injection, the tissues and organs of mice were more widely distributed compared with those of the wild mice(χ²=8.14, P < 0.05). Thirty minutes after injection, the ¹¹C-GF120918 radiation intensity in the brain and blood were still (99.3±0.5)% and (83.2±3.5)%, respectively, with better biochemistry and radiation stability. In PET studies, AUC_{brain0~60 min} in the P-gp knockout mice was nine times higher than that in the wild group(χ²=7.69, P < 0.05). The AUC_{brain0-60 min} of the BCPR knockout mice was three times higher than that in the wild group(χ²=8.24, P < 0.05). The evident effect of ¹¹C-GF120918 was relatively stable.

Conclusion ¹¹C-GF120918 can be used as PET probes to evaluate the multi-drug resistance of P-gp and BCRP.