Experimental study on tumor response to chemotherapy with 18F-SFB-Annexin B1 / 中国癌症杂志

ABSTRACT

Background and purpose: One of the main mechanism of chemotherapy is inducing tuomr apoptosis. Molecular imaging can allow noninvasively and dynamically monitor tumor apoptosis in vivo, and help to drug screening and therapeutic evaluation. The purpose of this study was to evaluate the feasibility of 18F-SFB-Annexin B1 in detecting apoptosis at an early phase after chemotheraphy. Methods:Annexin B1 was labeled with 18F using SFB as a chelating agent. Tissue distribution of 18F-SFB-Annexin B1 was studied in healthy mice by the dissection method. W256 tumor-bearing rats were injected with 18F-SFB-Annexin B1 intravenously at 24 h after the treatment of cyclophosphamide (CTX 200 mg/kg) or saline. Then imaging was acquired at 1, 2, 3, and 4 h postinjection on a PET/CT, and the tumor-to-muscle ratio of SUVmax (T/M) and the AI from TUNEL testing were compared. Results: 18F-SFB-Annexin B1 had a radiochemical pruity (RCP)>95%. Biodistribution of this probe showed a predominant uptake in the kidney, then was liver, spleen, and myocardium, rapid clearance from blood and urinary was observed. The radios of T/M were 4.38±0.56, 6.75±1.16, 6.44±1.12, 4.81±0.17, respectively at 1, 2, 3, 4 h post injection of the chemotherapy group, much higher than that of the saline group (2.35±0.14, 2.99±0.55, 3.04±0.41, 2.33±0.47, respectively). The differences between the two groups were significant (F=23.790, 16.913, 14.046, 77.517, respectively, all P<0.05). TUNEL staining revealed that chemotherapy treatment significantly increased the percentage of apoptosis cells with an AI of (21.00±0.04)%in the chemotherapy group, higher than that in the saline group (8.58±0.01)%, the difference was significant (F=21.539, P<0.05). The radios of T/M were significantly correlated with the values of AI (r=0.91, P<0.05). Conclusion: 18F-SFB-Annexin B1 can be used to apoptosis imaging and early therapeutic evaluation in vivo because it can reflect apoptosis at an early stage after chemotheraphy.