The Value Of ¹¹C-acetate PET/CT To Diagnose Renal Masses And The Researchs Of Related Mechanism

Part One The Value of 11C-acetate in Differential Diagnosis of Renal Masses Combined with 18F-FDGPurpose:Conventional imaging examinations are able to contribute to the diagnosis of renal cell carcinoma (RCC), but are still limited in differential diagnosis of renal masses. The sensitivity of diagnosing RCC using 18F-FDG PET is low. Some reports demonstrated the high 11C-acetate(11C-AC) uptake in RCC while the contradictory viewpoint in another similar research indicated that in most kidney tumors the 11C-acetate accumulation was not higher than in normal kidney parenchyma. The aim of this research is toinvestigate the value of 11C-AC PET/CT for differential diagnosis of renal masses.Method:34 patients with renal masses underwent dynamic PET imaging of the kidney for 20 minutes afterinjection of C-acetate and time-activity curves(TAC) were obtained in those positive lesions. The static images of 11C-acetate and 18F-FDG were acquired, and then the kidney lesions were scored positive or negative according to T/R> 1 or≤1. Fuhrman grade of RCC was evaluated and the express of fatty acid synthetase (FAS), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and Bcl-2 were determined by immunohistochemistry. The PET results were correlated with the histological diagnosis. The positive ratesof dual tracers were compared.Result:Among all the renal masses,26 cases were diagnosed by surgery,8 cases by biopsy.26 patients were confirmed the diagnosis of RCC, the positive rates of which were 88.5% and 38.5% by 11C-AC and 18F-FDG PET/CT with statistic difference (P<0.001). In the positive cases by both tracers, no difference was found in T/B between the 11C-AC and 18F-FDG PET/CT (1.78±0.50 vs 2.65±1.39, P=0.139). The peak time and tendency of TAC between RCCs and benign renal masses were obviously different. Furman grade was correlated with SUVmax in 18F-FDG PET/CT (r=0.667, P=0.005). The uptake of 11C-AC was higher in the RCCs with FAS-positive than those with FAS-negative (SUVmax4.79±1.16 vs.3.35±1.22,P=0.044; T/B 1.82 ±0.66 vs.1.24±0.27, P=0.049).Conclusion:The detective rate for RCC with 11C-AC PET/CT was higher than with 18F-FDG. TAC might be useful for differential diagnose renal masses.Part Two The Mechanism of 11C-acetate Uptake in Renal Cell Carcinoma and Related Experimental ResearchPurpose:The sensitivity of diagnosing renal cell carcinoma by 11C-acetate (11C-AC) PET/CT is higher than 18F-FDG. However, the mechanism of 11C-AC uptake in the tumor is not definite. It is reported that 11C-AC uptake may be related to; synthesis of fatty acid used to form cellular membrane. The aim is to identify the correlation between 11C-AC uptake and the expression of fatty acid synthase (FAS), which is key enzyme in the lipogenesis.Method:(1) In vitro cell uptake and inhibition:786-0, ACNH and Caki-1 (human renal carcinoma) were cultured, and then treated with a FAS inhibitor, C75 as experiment and with DMSO as control.30min after 11C-AC was added to cells, lysis extracts were counter in a y-counter and measured for protein content. Then, FAS expression was determined by Western blot. (2) Micro PET/CT:786-0-bearing nude mice were scanned by 11C-AC PET/CT and tumor to soft tissue ratios were measured. After imaging, the mice were euthanized, and the tumors were excised and immunohistochemical analysis. (3) Immunohistochemical analysis:After the cases with renal masses were imaged by 11C-AC PET/CT, immunohistochemical techniques were used to demonstrate the extent of FAS expression. Then, the correlation between 11C-AC uptake and FAS expression was analyzed.Result:(1) The 786-0 cells treated with C75 showed inhibition uptake by 31.42% (P=0.013) compared with control cells. No difference of 11C-AC uptake between treated cells and control cells for the ACNH and Caki-1 cell lines. Visual inspection of the Western blot results revealed obvious differences in the intensity of the band with the 786-0 cells, but no difference was found in the intensity of the bands with other two cell lines. (2) The tumor showed significant uptake in the mico PET/CT and strong positive in the immunohistochemical analysis of FAS expression. (3) No statistical difference of SUVmax and T/B was observed between the renal tumors with FAS positive and negative (P=0.57$). In the cases with clear cell carcinoma, the uptake of 11C-AC was higher in the tumor with FAS positive.Conclusion:The 11C-AC uptake in the primary sites of renal clear cell carcinoma was related to the expression of FAS, but different pathological type of renal tumor may utilize acetate through other metabolic pathways.Part Three The Influence of Radiation Enteritis on Predicting Pathological Response of Locally Advanced Rectal Cancer after Neoadjuvant Chemoradiation by PET/CTPurpose:Neoadjuvant chemoradiation (neoCRT) is proved to lower the risk of local recurrence and downstage the primary tumor of locally advanced rectal cancer (LARC). In recent years,18F-FDG PET/CT has been applied to monitor the response and distinguish pCR of LARC after neoCRT, but radiation enteritis (RE) may result in misestimating the tumor response. The objective of our prospective study was to investigate the value of PET/CT for evaluating the response to neoCRTin LARC and the influence of radiation enteritis on predicting the response.Methods:52 patients were diagnosed with LARC, treated with capecitabine-based chemoradiation and resection 6-8 weeks later.18F-FDG PET/CT was performed before and after CRT (PET1&2) in all patients and additional one before surgery (PET3) in 32 of whom. PET indices including SUVmax, SUVmean and volume were calculated by delineation of VOL Responders (TRG3-4) and non-responders (TRGO-2) were determined in histopathology. The correlation between pathological response and the percentage decreasein PET indices was analyzed in consideration of RE.Result:The pathological response rate was 40.4% (21/52 for TRG3-4). No significant differences in all the relevant PET parameters concluding the percentages of ASUVmax, ASUVmean and AMTV were observed between responders and non-responders (P=0.845,0.396 and 0.595). We found over half of patients suffered RE within one month after CRT, but most of them recovered before surgery. So, firstly, patients were divided into two groups according to with or without RE. In 31 patients with RE, absolute SUVmax in PET2 was a predictor of pathological response, which was significantly higher (P=0.034) in non-responders (7.51±1.97) than in responders (5.78±0.56). While, of 21 patients without RE, only the percentage of △SUVmean between PET1 and PET2 was significantly different (P=0.029) between nonresponders and responders. Secondly, we analyzed the parameters in PET3 and observed no correlation between the percentages of ASUVmax, ASUVmean, AMTV and pathological response (P=0.657,0.791,0.701).Conclusion:PET/CT after chemoradiation plays an important role in accessing the pathological response in LARC. Different parameters should be chosen for evaluating the response of CRT in consideration of radiation enteritis. PET/CT before surgery was not necessary for evaluating the response.