Chang Yi

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.

A Comparative Uptake Study of Multiplexed PET Tracers in Mice with Turpentine-Induced Inflammation

The potential value of multiplexed positron emission tomography (PET) tracers in mice with turpentine-induced inflammation was evaluated and compared with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) for glucose metabolism imaging. These PET tracers included [18F]fluoromethylcholine ([18F]FCH) for choline metabolism imaging, (S-[11C]methyl)-D-cysteine ([11C]DMCYS) for amino acid metabolism imaging, [11C]bis(zinc(II)-dipicolylamine) ([11C]DPA-Zn2+) for apoptosis imaging, 2-(4-N-[11C]-methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB) for β amyloid binding imaging, and [18F]fluoride (18F−) for bone metabolism imaging. In mice with turpentine-induced inflammation mice, the biodistribution of all the tracers mentioned above at 5, 15, 30, 45, and 60 min postinjection was determined. Also, the time-course curves of the tracer uptake ratios for inflammatory thigh muscle (IM) to normal uninflammatory thigh muscle (NM), IM to blood (BL), IM to brain (BR), and IM to liver (LI) were acquired, respectively. Moreover, PET imaging with the tracers within 60 min postinjection on a clinical PET/CT scanner was also conducted. [18F]FDG and 18F− showed relatively higher uptake ratios for IM to NM, IM to BL, IM to BR, and IM to LI than [18F]FCH, [11C]DPA-Zn2+, [11C]DMCYS and [11C]PIB, which were highly consistent with the results delineated in PET images. The results demonstrate that 18F− seems to be a potential PET tracer for inflammation imaging. [18F]FCH and [11C]DMCYS, with lower accumulation in inflammatory tissue than [18F]FDG, are not good PET tracers for inflammation imaging. As a promising inflammatory tracer, the chemical structure of [11C]DPA-Zn2+ needs to be further optimized.

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.

Human radiation dose estimation of (11)C-CFT using whole-body PET.

Purpose 11C-Labeled 2-&bgr;-carbomethoxy-3-&bgr;-(4-fluorophenyl)tropane (11C-CFT) is a commonly used positron emission tomography (PET) tracer for dopamine transporters imaging. The present study estimated human radiation absorbed doses of 11C-CFT based on whole-body PET imaging in healthy subjects. Methods Whole-body PET was performed on 6 subjects after injection of 472.06 ± 116.47 MBq of 11C-CFT. 7 Frames were acquired for about 70 min in 7 segments of the body. Regions of interest were drawn on PET images of source organs. Residence time was calculated as the area under the time-activity curve. Radiation dosimetry was calculated from organ residence time using the medical internal radiation dosimetry (MIDR) method. Results The organs with the highest radiation-absorbed doses were the urinary bladder, followed the spleen, pancreas, kidneys, and stomach. The dose-limiting critical organ was the urinary bladder. The effective dose was 8.89E−03 mSv/MBq (22.9 mrem/mCi). Biexponential fitting of mean bladder activity demonstrated that 18% of activity was excreted via the urine. Conclusions The potential radiation risks of 11C-CFT associated with in this study are well within accepted limits. 11C-CFT demonstrates a favorable radiation dose profile in humans and allows multiple PET examinations on the same subject per year.

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.

Efficient preparation of [11C]CH3Br for the labeling of [11C]CH3-containing tracers in positron emission tomography clinical practice.

Background and aim[11C]methyl iodide ([11C]CH3I) is the most extensively used methylation agent for the preparation of a majority of 11C-labeled positron emission tomography (PET) radiotracers, which is commonly produced by the wet method and the gas-phase method. On account of the complexity of the gas-phase method, a simple automated synthesis of [11C]methyl bromide ([11C]CH3Br) as an analog of [11C]CH3I is derived by the wet method in this study. Radiosynthesis of L-[S-methyl-11C]methionine (MET), L-[S-methyl-11C]cysteine (MCYS), [N-methyl-11C]choline (CH), [11C]methyl triflate ([11C]CH3OSO2CF3), and [11C]-2-&bgr;-carbomethoxy-3-&bgr;-(4-fluorophenyl)-tropane (CFT) by methylation reaction with [11C]CH3Br, and PET imaging of patients are also described. MethodsThe preparation of [11C]CH3Br by a one-pot wet method involved the following steps: reduction of [11C]carbon dioxide with lithium aluminium hydride (LiAlH4) solution, treatment with hydrobromic acid, and distillation of [11C]CH3Br under continuous nitrogen flow. [11C]methylation of L-homocysteine thiolactone hydrochloride, L-cysteine, 2-dimethylaminoethanol, silver triflate, and nor-&bgr;-CFT as precursors with [11C]CH3Br and purification with Sep-Pak cartridges gave MET, MCYS, CH, [11C]CH3OSO2CF3, and CFT, respectively. In addition, PET imaging of brain cancer and Parkinsons disease was carried out. ResultsThe uncorrected radiochemical yield of [11C]CH3Br was (37.8±2.5%) based on [11C]carbon dioxide within a total synthesis time of 10 min and the radiochemical purity of [11C]CH3Br was greater than 95%. The uncorrected yields of MET, MCYS, CH, [11C]CH3OSO2CF3, and CFT were 70.1±0.5%, 70.2±2.3%, 60.3±1.8%, 95.1±2.2%, and 60.1±1.5% (from [11C]CH3OSO2CF3) within a total synthesis time of 2, 2, 5, 1, and 8 min, respectively. The radiochemical purity of MET, MCYS, CH, [11C]CH3OSO2CF3, and CFT was more than 95%. Good PET images in the patients are obtained. ConclusionAutomated synthesis of [11C]CH3Br can be done by the wet method on the commercial [11C]CH3I synthesizer. [11C]CH3Br can be used for a [11C]methylation reaction to produce 11C-labeled tracers for clinical PET imaging.

The combination of 13N-ammonia and 18F-FDG whole-body PET/CT on the same day for diagnosis of advanced prostate cancer.

PurposeThe aim of the study was to evaluate the efficacy of 13N-ammonia and 18F-fluorodeoxyglucose (18F-FDG) PET performed on the same day in the detection of advanced prostate cancer (PC) and its metastases. Patients and methodsTwenty-six patients with high-risk PC [Gleason score 8–10 or prostate-specific antigen (PSA)>20 ng/ml or clinical tumor extension≥T2c] were recruited into the study. 13N-Ammonia and 18F-FDG PET/CT were performed on the same day (18F-FDG followed ammonia, with an interval of a minimum of 2 h). Lesions were interpreted as positive, negative, or equivocal. Patient-based and field-based performance characteristics for both imaging techniques were reported. ResultsThere was significant correlation between 13N-ammonia and 18F-FDG PET/CT in the detection of primary PC (&kgr;=0.425, P=0.001) and no significant difference in sensitivity (60.2 vs. 54.5%) and specificity (100 vs. 83.3%). The maximum standard uptake values and corresponding target-to-background ratio values of the concordantly positive lesions in prostate glands in the two studies did not differ significantly (P=0.124 and 0.075, respectively). The sensitivity and specificity of PET imaging using 13N-ammonia for lymph node metastases were 77.5 and 96.3%, respectively, whereas the values were 75 and 44.4% using 18F-FDG. The two modalities were highly correlated with respect to the detection of lymph nodes and bone metastases. ConclusionThe concordance between the two imaging modalities suggests a clinical impact of 13N-ammonia PET/CT in advanced PC patients as well as of 18F-FDG. 13N-Ammonia is a useful PET tracer and a complement to 18F-FDG for detecting primary focus and distant metastases in PC. The combination of these two tracers on the same day can accurately detect advanced PC.