PET/CT Imaging Of Angiogenesis Based On ¹⁸F-RGD PET/CT Tracer Uptake May Be Useful For Predicting Response To Antiangiogenic Treatment

PurposeThe survival,growth and metastasis of solid tumors highly depend on the angiogenesis,and the therapeutic effect of antiangiogenic therapy on various types of tumor is remarkable.However,there were significant differences in the efficacy and the adverse effects?AEs?of antiangiogenic therapy among different patients.Therefore,early prediction of the effect and AEs of antiangiogenic therapy is particularly important for screening of antiangiogenic therapy and AEs individually.This study aims to explore the relationship between metabolic uptake of the ¹⁸F-ALF-NOTA-PRGD2(¹⁸F-RGD)tracer on positron emission tomography/computerized tomography?PET/CT?and the antiangiogenic effect and AEs of apatinib in patients with solid malignancies.Materials and patientsPatients with measurable lesions scheduled for second-or third-line single-agent therapy with apatinib were eligible for this prospective clinical trial.All patients underwent ¹⁸F-RGD PET/CT examination before the start of treatment.The peak,maximum and mean standardized uptake values(SUV_peak,SUV_max and SUV_mean)of tumor lesions were processed with an automated contouring program using a threshold SUV of 2.5.SUV_max and SUV_meanean were obtained in regions of interest within normal structures.Standardized uptake values?SUVs?of contoured tumor lesions and normal structures were computed and compared using independent sample t-tests or Mann-Whitney U test.Receiver-operating characteristic?ROC?curve analysis was used to determine accuracy in predicting response.The chi-square test??²test?was used to test the composition ratio.Survival curves were compared using the Kaplan-Meier and Log-rank method.ResultsOf 38 patients who consented to study participation,25 patients with 42 measurable lesions met the criteria for inclusion in this response assessment analysis.The median follow-up time was 3 months?range,1–10 months?,and the median progression-free survival?PFS?was 3months?95%confidence interval,1.04–4.96?.The SUV_peak and SUV_mean were significantly higher in responding tumors than in non-responding tumors?4.98±2.34 vs.3.59±1.44,P=0.048;3.71±1.15 vs.2.95±0.49,P=0.036?.SUV_max did not differ between responding tumors and non-responding tumors?6.58±3.33 vs.4.74±1.83,P=0.078?.An exploratory ROC curve analysis indicated that SUV_mean?area under the ROC curve[AUC]=0.700?was a better parameter than SUV_peak?AUC=0.689?for predicting response.Using a threshold value of3.82,high SUV_mean at baseline was associated with improved PFS?5.0 vs.3.4 months,log-rank P=0.036?.The three most frequently occurring AEs at the 1-month follow-up for the 30 included patients were fatigue,hypertension,and nausea.Max and mean SUVs of thyroid and liver were significantly associated with fatigue,while SUVs of thyroid,part of stomach,and spleen for hypertension,and SUVs of thyroid,stomach,spleen,and liver for nausea?all P<0.05?.According to the ROC curve analysis,the most significant predictors of AEs were ¹⁸F-RGD SUV_max-liver for fatigue?area under the ROC curve[AUC]=0.789?,SUV_max-spleen for hypertension?AUC=0.815?,and SUV_max-cardia for nausea?AUC=0.909?.The threshold values for SUV_max-liver,SUV_max-spleen,and SUV_max-cardia were 4.57,6.41,and 2.20,respectively.Chi-Square test showed that the incidence of fatigue,hypertension and nausea in patients with low SUV_max values of liver,spleen and cardia were statistically higher than patients with high uptake?P<0.01?.Conclusion¹⁸F-RGD uptake on PET/CT imaging pretreatment may predict the response and AEs to antiangiogenic therapy,with higher ¹⁸F-RGD uptake in tumors predicting a better response and normal structures predicting reduced risks of AEs to apatinib therapy.