Assessment of renal cell carcinoma by two PET tracer : dual-time-point C-11 methionine and F-18 fluorodeoxyglucose

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Assessment of renal cell carcinoma by two PET tracer : dual-time-point C-11 methionine and F-18 fluorodeoxyglucose Poster No.: C-0805 Congress: ECR 2015 Type: Scientific Exhibit Authors: S. Ito, K. Kato, T. Okuda, S. Maeda, S. Naganawa ; Nagoya/ 1 1 2 2 1 1 2 JP, Toyota/JP Keywords: Nuclear medicine, Oncology, Kidney, PET-CT, Diagnostic procedure, Cancer DOI: 10.1594/ecr2015/C-0805 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 16

Aims and objectives Earlier studies demonstrated that F-18 fluoro-deoxyglucose (FDG) PET have lower sensitivity (50-60 %) in detecting renal cell carcinoma (RCC) compared with other malignant tumors. The reasons for low sensitivity are considered to be due to decreased contrast between tumor and normal renal tissue caused by renal excretion of FDG and 1,2) high activity of glucose-6-phosphatase in RCC. C-11 methionine has been used for PET imaging to assess the amino acid metabolism in tumors. It is well established that Met-PET is effective in gliomas for detecting tumors, evaluating the response of treatment, and differentiating between tumor recurrence and radiation necrosis. It has been also reported that FDG and Met are equally useful for detecting residual and recurrent tumors and differentiating benign tumors from head and 3) 4) neck cancer, and lung cancer. We prospectively assessed usefulness of dual-time-point C-11 methionine PET (MetPET) and F-18 fluorodeoxyglucose PET (FDG-PET) for renal cell carcinoma (RCC). Page 2 of 16

Methods and materials Eleven patients (8 males, 3 femeles; age 44 to 76y, mean ages 59 ± 11y) suspected of RCC with abdominal ultrasonography and CT were enrolled. All patients agreed to participate in this study. The Medical Ethics Committee of Toyota Memorial Hospital approved the study protocol. FDG-PET and Met-PET scans were performed within the interval of 1 week for all the patients. All the patients were diagnosed as renal cell carcinoma histopathologically. Met-PET scan was performed 5 minutes (early-phase) and 30 minutes (delayedphase) after administration of Met. FDG-PET scan was performed 60 minutes after administration of FDG. All patients underwent both Met-PET and FDG-PET within one month before the surgical operation. We measured the maximum standardized uptake value (SUVmax) of RCC lesion with Met-PET (early- and delayed-phase) and FDG-PET. All patients were clinically and radiographically followed up for more than one year after the surgical operation. Paired t-test was used in comparison between the uptake of MET and FDG for statistical analysis. Page 3 of 16

Results The surgical operation (10 total nephrectomy and 1 partial nephrectomy) was performed within 1 month after PET scan. Eleven lesions of eleven patients were resected and pathologically diagnosed as RCC. The histopathological subtype and grading were shown in Table 1. The size of all tumors was over 10mm (range: 17-90mm, mean 48mm). Neither metastasis in the regional lymphnodes nor distant metastasis were found in all patients when nephrectomy was performed. Both Met and FDG accumulated in all RCC lesions. The SUVmax of RCC lesions in the early-phase Met-PET, delayed-phase Met-PET, and FDG-PET were 4.6±2.3, 3.1±1.0, and 2.6±1.0, respectively. The SUVmax of the early- phase Met-PET showed significantly higher values than that of the delayed- phase Met-PET (p = 0.016) and that of FDG-PET (p = 0.022). On the other hand, there was no significant difference between the SUVmax of the delayed-phase Met-PET and that of FDG-PET (p = 0.132) [Fig. 1]. During the follow-up period, lung metastases were detected in two patients [Fig.2-6]. In these two patients, SUVmax of the early-phase Met-PET of RCC showed over 5.0, and it was higher than SUVmax in patients with no metastases, except for one patient whose value was 11.0 [Table 2]. SUVmax of the delayed-phase Met-PET and FDG-PET of two patients whose metastases were detected also showed higher value than any SUVmax of patients whose metastases were not detected, whereas all of the values indicated under 4.5. Page 4 of 16

Images for this section: Table 1: Histopathologic subtype and grading of patients. Page 5 of 16

Fig. 1: The SUVmax of RCC lesions in the early-phase (5 min) Met-PET, delayed phase (30 min) Met-PET, and FDG-PET. The SUVmax of the early- phase Met-PET showed significantly higher values than that of the delayed- phase Met-PET and that of FDG-PET. Page 6 of 16

Fig. 2: A case of 55-year-old male, clear cell RCC in the left kidney #pt2an0m0, grade 3). Contrast enhanced CT image demonstrated a mass with 9.5cm in size located in the left kidney. Page 7 of 16

Fig. 3: Delayed-phase Met-PET showed high uptake in the tumor. The SUVmax of the tumor indicated 4.5. Page 8 of 16

Fig. 4: FDG-PET also showed high uptake in the tumor. The SUVmax of the tumor indicated 3.6. Page 9 of 16

Fig. 5: One year later, multiple metastases were found in the bilateral lungs in CT. Page 10 of 16

Table 2: The SUVmax of MET and FDG in cases with and without recurrence during follow-up period. Page 11 of 16

Conclusion In PET image of RCC, the early-phase Met-PET showed a significantly higher uptake than FDG-PET [Fig. 6-8]. This suggests that we can detect RCC lesions more distinctly with Met-PET than with FDG-PET. In our Met-PET imaging, the image obtained in the early-phase showed a significantly higher uptake than that obtained in the delayed-phase. Met uptake in multi-phase or dynamic state for tumors was reported in a few studies. Aki et al. reported three-phase 5) Met uptake for several kinds of brain tumors. They showed that dynamic decrease was seen in meningioma and oligodendrocytic tumors, whereas increase was seen in glioblastoma and malignant lymphoma. Toth et al. reported that short dynamic Met 6) scanning is a useful method for ensuring the location of prostate cancer. They showed that the time-activity curve of prostate cancer demonstrated plateau from 5 minutes to 50 minutes, while the curve of normal prostate tissue had a high peak around 5 minutes and then decreased until 50 minutes. In RCC, both Met and FDG uptakes are often similar to normal renal tissue. Additionally, in the present study, 10 of 11 lesions histoparhologically diagnosed as grade 1 or 2, and only 1 lesion was grade 3. The results of higher uptake in the early phase than in the delayed phase suggest that RCC has similar metabolic activities to normal renal tissue in amino acid metabolisms. In conclusion, Met-PET image in the early-phase may provide more useful information about the diagnosis of RCC. Page 12 of 16

Images for this section: Fig. 6: A case of 47-year-old male, chromophobe RCC in the right kidney #pt2bn0m0, grade 2). Contrast enhanced CT image demonstrated a mass with 12.5cm in size located in the right kidney. Page 13 of 16

Fig. 7: Early-phase Met-PET showed high uptake in the tumor. The SUVmax of the tumor indicated 4.6. Page 14 of 16

Fig. 8: FDG-PET showed low uptake in the tumor. The SUVmax of the tumor indicated 1.6. Page 15 of 16

References 1. 2. 3. 4. 5. 6. Kang DE, White RL Jr., Zuger JH, Sasser HC, Teigland CM. Clinical use of fluorodeoxyglucose F-18 positron emission tomography for detection of renal cell carcinoma. J Urol. 2004; 171: 1806-1809 Nicolas Aide, Olivier Cappele, et al. Efficacy of F-18 FDG PET in charactering renal cell cancer and distant metastases. Eur J Nucl Mol Imaging 2003; 30: 1236-1245 Lindholm P, et al. Comparison of F-18 FDG and C-11 methionine in head and neck cancer. J Nucl Med. 1993; 34: 1711-1716 Sasaki M, Kuwabara Y, et al. Comparison of MET-PET and FDG-PET for differentiation between benign lesions and malignant tumors of the lung. Ann Nucl Med 2001; 15: 425-431 Aki T, Nakayama N, et al. Evaluation of brain tumors using dynamic C-11 methionine PET. J Neurooncol. 2012; 109: 115-122 Toth G, Lengyel Z, et al. Detection of prostate cancer with C-11 methionine positron emission tomography. J Urol. 2005; 173: 66-69 Page 16 of 16