Xinchong Shi

S-11C-Methyl-L-Cysteine: A New Amino Acid PET Tracer for Cancer Imaging

S-11C-methyl-L-cysteine (11C-MCYS), an analog of S-11C-methyl-L-methionine (11C-MET), can potentially serve as an amino acid PET tracer for tumor imaging. The aim of this study was to investigate the radiosynthesis and perform a biologic evaluation of 11C-MCYS as a tumor imaging tracer. The results of the first human PET study are reported. Methods: 11C-MCYS was prepared by 11C-methylation of the precursor L-cysteine with 11CH3I and purification on commercial C18 cartridges. In vitro competitive inhibition experiments were performed with Hepa1–6 hepatoma cell lines, and biodistribution of 11C-MCYS was determined in normal mice. The incorporation of 11C-MCYS into tissue proteins was investigated. In vivo 11C-MCYS uptake studies were performed on hepatocellular carcinoma–bearing nude mice and inflammation models and compared with 11C-MET PET and 18F-FDG PET. In a human PET study, a patient with a recurrence of glioma after surgery was examined with 11C-MCYS PET and 18F-FDG PET. Results: The uncorrected radiochemical yield of 11C-MCYS from 11CH3I was more than 50% with a synthesis time of 2 min, the radiochemical purity of 11C-MCYS was more than 99%, and the enantiomeric purity was more than 90%. In vitro studies showed that 11C-MCYS transport was mediated through transport system L. Biodistribution studies demonstrated high uptake of 11C-MCYS in the liver, stomach wall, and heart and low uptake of 11C-MCYS in the brain. There was higher accumulation of 11C-MCYS in the tumor than in the muscles. The tumor-to-muscle and inflammatory lesion–to–muscle ratios were 7.27 and 1.62, respectively, for 11C-MCYS, 5.08 and 3.88, respectively, for 18F-FDG, and 4.26 and 2.28, respectively, for 11C-MET at 60 min after injection. Almost no 11C-MCYS was incorporated into proteins. For the patient PET study, high uptake of 11C-MCYS with true-positive results, but low uptake of 18F-FDG with false-negative results, was found in the recurrent glioma. Conclusion: Automated synthesis of 11C-MCYS is easy to perform. 11C-MCYS is superior to 11C-MET and 18F-FDG in the differentiation of tumor from inflammation and seems to have potential as an oncologic PET tracer for the diagnosis of solid tumors.

The combination of 13N-ammonia and 18F-FDG in predicting primary central nervous system lymphomas in immunocompetent patients.

Objective Accurate identification of primary central nervous system lymphoma (PCNSL) and its differentiation from other brain tumors remain difficult but are essential for treatment. In this study, we investigated whether 13N-ammonia combined with 18F-FDG could distinguish PCNSL from solid gliomas effectively. Methods Ten consecutive patients with final diagnosis of PCNSL (5 female and 5 male patients; mean [SD] age, 59.10 [12.47] years; range, 43–74 years) and another fifteen consecutive patients with solid glioma lesions (5 female and 10 male patients; mean [SD] age, 46.73 [19.61] years; range, 14–72 years) were included in this study. PET/CT imaging was performed for all of them with both 18F-FDG and 13N-ammonia as tracers. Tumor-to-gray matter (T/G) ratios were calculated for the evaluation of tumor uptake. Both Student t test and discriminant analysis were recruited to assess the differential efficacy of these 2 tracers. Results The T/G ratios of 18F-FDG in PCNSL lesions were higher than in solid gliomas (3.26 [1.18] vs 1.56 [0.41], P < 0.001), whereas the T/G ratios of 13N-ammonia in PCNSL lesions were lower than in solid gliomas significantly (1.38 [0.20] vs 2.11 [0.69], P < 0.001). All the lesions of PCNSL displayed higher T/G ratios of 18F-FDG than 13N-ammonia, whereas 14 (77.8%) of 18 glioma lesions showed contrary results. Tumor classification by means of canonical discriminant analysis yielded an overall accuracy of 96.9%, and only one glioma lesion was misclassified into the PCNSL group. Conclusions PCNSLs and solid gliomas have different metabolic profiles on 13N-ammonia and 18F-FDG imaging. The combination of these 2 tracers can distinguish these 2 clinical entities effectively and make an accurate prediction of PCNSL.

13N-ammonia combined with 18F-FDG could discriminate between necrotic high-grade gliomas and brain abscess.

Purpose Accurate prediction of brain abscess is beneficial for timely management. In this study, we investigated the utility of 13N-ammonia and its combination with 18F-FDG in differentiating brain abscess from necrotic high-grade gliomas. Patients and Methods Thirteen patients with ring-like enhancement high-grade gliomas and 11 patients with brain abscess were recruited in our study. All of them underwent both 18F-FDG and 13N-ammonia PET imaging. Lesion uptake was evaluated by lesion to normal gray matter ratio (L/N). Histopathology diagnosis was obtained for all the patients after PET imaging. Results The L/N values of 18F-FDG were not significantly different between brain abscess and necrotic high-grade gliomas (P = 0.35). The uptake of 13N-ammonia in gliomas was higher than that in abscess lesions (L/N: 1.38 ± 0.31 vs 0.84 ± 0.18, P < 0.001). The receiver operating characteristic curve analysis determined the optimal L/N cutoff value (13N-ammonia) of 1.0 with the area under the curve of 0.94 and the overall accuracy of 87.5%. Discriminant analysis demonstrated that the combination of 18F-FDG and 13N-ammonia could distinguish the 2 clinical entities with higher accuracy of 95%, and only 1 necrotic glioma lesion was misclassified into the abscess group. Conclusions 13N-ammonia is effective in distinguishing brain abscess from necrotic high-grade gliomas, and its combination with 18F-FDG could further elevate the diagnostic accuracy.

Hepatic tuberculosis mimics metastasis revealed by 18F-FDG PET/CT.

Extrapulmonary tuberculosis can affect almost any organ in the body. Here, we report a rare case of primary hepatic tuberculosis presented as multiple hepatic lesions and enlarged lymph nodes in the retroperitoneum and porta hepatis. PET/CT imaging showed avid FDG uptake by these lesions but did not find any definite primary malignancy. Finally, a diagnosis of primary hepatic tuberculosis was made with histopathologic examination.

The comparison of 13N-ammonia and 18F-FDG in the evaluation of untreated gliomas.

Objective Noninvasive evaluation of glioma is of great help for clinical practice. In this study, we investigated the utility of 13N-ammonia in the evaluation of untreated gliomas and compared the results with that of 18F-FDG. Methods Forty-five consecutive patients with final diagnosis of glioma were included in this study. PET/CT imaging was performed for all of them with both 18F-FDG and 13N-ammonia as tracers. Imaging results were analyzed by tumor-to-gray matter (T/G) ratios. Receiver operating characteristic curve analysis was conducted to determine the optimal T/G cutoff values of each tracer between low-grade and high-grade gliomas. Results Forty-eight separate lesions were identified in all (grade II, n = 16; grade III, n = 12; and grade IV, n = 20). Twenty-nine out of 32 high-grade lesions (91%) showed higher uptakes than normal gray matter with 13N-ammonia in comparison with the result of 21 lesions (66%) with 18F-FDG. The optimal T/G cutoff values for 18F-FDG and 13N-ammonia were 0.64 and 0.86 separately with the area under each curve 0.910 and 0.943. The sensitivity and specificity of predicting high-grade gliomas with optimal cutoff values were 83% and 93% for 18F-FDG and 94% and 94% for 13N-ammonia, respectively. Conclusion 13N-Ammonia is superior to 18F-FDG not only in separating low-grade gliomas from high-grade ones but also in the detection of high-grade gliomas for better tumor to normal gray matter contrast.

18F-FDG PET/CT Findings in Multicentric Reticulohistiocytosis.

Multicentric reticulohistiocytosis is a rare systemic inflammatory disease of unknown etiology characterized by the infiltration of histiocytes and multinucleated giant cells into multiple systems. The definitive diagnosis depends on biopsy of the affected tissues. Here, we report the F-FDG PET/CT findings of a 62-year-old man with multicentric reticulohistiocytosis. Increased FDG uptake was observed in cutaneomucosal papules, surrounding tissues of many joints, multiple muscles, and lymph nodes.

The alteration of 18F-FDG uptake in bone marrow after treatment with interleukin 11.

Diffuse increased F-FDG in the bone marrow can be seen with colony-stimulating factors. Here, we reported a case of idiopathic cytopenia of undetermined significance treated with interleukin 11. After administration of interleukin 11, both diffuse and focally increased FDG activity in the bone marrow were noted. The focal activity was histologically proven as hyperplastic bone marrow.

The influence of residual nor-β-CFT in 11C CFT injection on the Parkinson disease diagnosis: a 11C CFT PET study.

Purpose Fully automated synthesis of 11C–labeled 2&bgr;-carbomethoxy-3&bgr;-(4-fluorophenyl)tropane (11C CFT) as a dopamine transporter positron emission tomography (PET) tracer is performed with Sep-Pak purification, which cannot separate 11C CFT from nor-&bgr;-CFT and will result in the residual precursor nor-&bgr;-CFT in the final 11C CFT injection. The aim of this study is to estimate the influence of the residual precursor nor-&bgr;-CFT in the 11C CFT injection on the Parkinson disease (PD) diagnosis results. Methods Automated synthesis of 11C CFT was performed using the different chemical amounts (0.10, 0.20, 0.25, and 0.30 mg) of nor-&bgr;-CFT with Sep-Pak purification. According to the given different amounts of nor-&bgr;-CFT in the radiosynthesis, clinically suspected 25 PD patients were randomly divided into the following 4 groups: 0.10 mg, 0.20 mg, 0.25 mg, and 0.30 mg, which had 5, 9, 5, and 6 cases, respectively. A normal control group with 0.10 mg of nor-&bgr;-CFT included 2 volunteers. After the brain PET images of the subjects were acquired, the regions of interests of striatum and cerebellum were drawn, and the standard uptake values of these regions were calculated. Finally, comparing the 18F FDG PET and clinical diagnosis, the coincidence rates of 11C CFT PET imaging for PD patients were determined. Results Given 0.25 mg of the precursor nor-&bgr;-CFT, high radiochemical yield (59.4%) and high radiochemical purity of 11C CFT were obtained using Sep-Pak purification within a short synthesis time. The 11C CFT standard uptake value ratios of striatum to cerebellum had no statistically significant difference (P > 0.05) between the 4 suspected PD groups. However, there was statistically significant difference (P < 0.05) between the suspected PD groups and the control group. Also, the coincidence rates between the PD diagnosis using 11C CFT PET imaging for different dose groups and the final clinical diagnosis result were greater than 80%, but difference between the coincidence rates was not statistically significant (P = 0.955). Conclusions A simple, rapid, and efficient automated synthesis of 11C CFT using 0.25 mg of nor-&bgr;-CFT with Sep-Pak purification is afforded, providing enough radioactivity for PD PET imaging routinely. The residual nor-&bgr;-CFT in the 11C CFT injection is not inhibit 11C CFT binding to dopamine transporter, and also has no influence on PET diagnosis results of PD.

Human Biodistribution and Radiation Dosimetry of S-11C-Methyl-L-Cysteine Using Whole-Body PET.

Purpose S-11C-Methyl-L-cysteine (11C-MCYS) is a recently developed amino acid PET tracer for tumor imaging. The present study estimated human radiation absorbed dose of 11C-MCYS in healthy volunteers based on whole-body PET imaging. Methods Five sequential whole-body PET scans were performed on 6 healthy volunteers after injection of 11C-MCYS. Each scan contained of approximately 7 to 10 bed positions, and total scan time of each volunteer was approximately 70 to 85 minutes. Regions of interest were drawn on PET images of source organs. Residence times of 13 source organs for men and 14 source organs for women were calculated from the organ-specific time-activity curves. Absorbed dose estimates were performed from organ residence time by using the medical internal radiation dosimetry method. Results All volunteers showed initial high uptake in liver, heart, kidneys, pancreas, spleen, and uterus (only women), and followed by rapid clearance. There was very little activity residual in most of the organs except for the liver at the last emission scan time (approximately 75 minutes). The liver was the dose-limiting critical organ with the highest radiation-absorbed dose (1.01E-02 ± 2.64E-03 mGy/MBq), followed by the heart (9.09E-03 ± 1.40E-03 mGy/MBq), and the kidneys (7.12E-03 ± 9.44E-04 mGy/MBq). The effective dose to the whole body was 4.03E-03 ± 1.65E-04 mSv/MBq. A routine injection of 555 MBq (15 mCi) of 11C-MCYS would lead to an estimated effective dose of 2.24 ± 0.092 mSv. Conclusions The potential radiation risks associated with 11C-MCYS PET imaging are within accepted limits. 11C-MCYS is a safe amino acid PET tracer for tumor imaging and can be used in further clinical studies.

Recurrent Scapular Metastasis From Hepatoblastoma Shown on Fdg Pet/ct and F-dopa Pet/ct

We report the case of a 4-year-old girl with a biochemical relapse (plasma α-fetoprotein of 57,987.6 μg/L) after hepatoblastoma and extrahepatic metastases removal and adjuvant chemotherapy. Abdominal ultrasound, CT, and MRI failed to determine the site of recurrence. F-FDG PET/CT showed increased activity in the region of left scapula and adjacent soft tissue, which was incorrectly interpreted as the postoperative repair or inflammatory change. F-DOPA PET/CT showed increased activity and noticeable progressed lesion in the same place. Finally, the left scapula was identified as the site of recurrent metastasis from hepatoblastoma by pathological examination.