Development of [18F]AlF-NOTA-NT as PET Agents of Neurotensin Receptor-1 Positive Pancreatic Cancer.

Several studies have suggested that neurotensin receptors (NTRs) and neurotensin (NT) greatly affect the growth and survival of pancreatic ductal adenocarcinoma (PDAC). Developing NTR-targeted PET probes could therefore be important for the management of a pancreatic cancer patient by providing key information on the NTR expression profile noninvasively. Despite the initial success on the synthesis of 18F-labeled NT PET probes, the labeling procedure generally requires lengthy steps including azeotropic drying of 18F. Using a straightforward chelation method, here we report the simple preparation of aluminum-18F-NOTA-NT starting from aqueous 18F. The cell binding test demonstrated that [19F]AlF-NOTA-NT maintained high receptor-binding affinity to NTR1. This probe was then further evaluated in NTR1 positive pancreatic tumor models (AsPC-1 and PANC-1). After the administration of [18F]AlF-NOTA-NT, small animal PET studies showed a high contrast between tumor and background in both models at 1 and 4 h time points. A blocking experiment was performed to demonstrate the receptor specificity: the tumor uptake in AsPC1 without and with blocking agent was 1.0 ± 0.2 and 0.1 ± 0.0%ID/g, respectively, at 4 h post injection. In summary, a NTR specific PET agent, [18F]AlF-NOTA-NT, was prepared through the simple chelation method. This NTR-targeted PET probe may not only be used to detect NTR1 positive pancreatic tumors (diagnosis), but also it may be fully integrated to NTR target therapy leading to personalized medicine (theranostic).

Imaging Neurotensin Receptor in Prostate Cancer With 64Cu-Labeled Neurotensin Analogs.

INTRODUCTION: Neurotensin receptor 1 (NTR-1) is expressed and activated in prostate cancer cells. In this study, we explore the NTR expression in normal mouse tissues and study the positron emission tomography (PET) imaging of NTR in prostate cancer models. MATERIALS AND METHODS: Three 64Cu chelators (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid [DOTA], 1,4,7-triazacyclononane-N,N',N″-triacetic acid [NOTA], or AmBaSar) were conjugated to an NT analog. Neurotensin receptor binding affinity was evaluated using cell binding assay. The imaging profile of radiolabeled probes was compared in well-established NTR+ HT-29 tumor model. Stability of the probes was tested. The selected agents were further evaluated in human prostate cancer PC3 xenografts. RESULTS: All 3 NT conjugates retained the majority of NTR binding affinity. In HT-29 tumor, all agents demonstrated prominent tumor uptake. Although comparable stability was observed, 64Cu-NOTA-NT and 64Cu-AmBaSar-NT demonstrated improved tumor to background contrast compared with 64Cu-DOTA-NT. Positron emission tomography/computed tomography imaging of the NTR expression in PC-3 xenografts showed high tumor uptake of the probes, correlating with the in vitro Western blot results. Blocking experiments further confirmed receptor specificity. CONCLUSIONS: Our results demonstrated that 64Cu-labeled neurotensin analogs are promising imaging agents for NTR-positive tumors. These agents may help us identify NTR-positive lesions and predict which patients and individual tumors are likely to respond to novel interventions targeting NTR-1.

Evaluation of neurotensin receptor 1 as a potential imaging target in pancreatic ductal adenocarcinoma.

Pancreatic cancer is one of the deadliest human malignancies and lack of effective diagnostic and therapeutic methods. Accumulating evidence suggests that the neurotensin (NT) and neurotensin receptors (NTRs) play key roles in pancreatic adenocarcinoma growth and survival. In this study, we not only evaluate the NTR1 expression in pancreatic cancer patient samples, but also explore the PET and fluorescence imaging of NTR1 expression in pancreatic cancer animal models. The NTR1 expression was evaluated by immunohistochemistry staining in clinical patient tissue samples with pancreatic ductal adenocarcinoma, insulinoma, and pancreatitis. The results showed 79.4% positive rate of NRT1 expression in pancreatic ductal adenocarcinoma, compared with 33.3 and 22.7% in insulinoma and pancreatitis samples, respectively. High NTR1 gene expression was also found in Panc-1 cells and confirmed by cell immunofluorescence. 64Cu-AmBaSar-NT and IRDye800-NT were synthesized as imaging probes and maintained the majority of NTR1-binding affinity. In vivo imaging demonstrated that 64Cu-AmBaSar-NT has prominent tumor uptake (3.76 ± 1.45 and 2.29 ± 0.10%ID/g at 1 and 4 h post-injection). NIR fluorescent imaging with IRDye800-NT demonstrated good tumor-to-background contrast (8.09 ± 0.38 × 108 and 6.67 ± 0.43 × 108 (p/s/cm2/sr)/(µW/cm2) at 30 and 60 min post-injection). Fluorescence guided surgery was also performed as a proof of principle experiment. In summary, our results indicated that NTR1 is a promising target for pancreatic ductal adenocarcinoma imaging and therapy. The imaging probes reported here may not only be considered for improved diagnosis of pancreatic ductal adenocarcinoma, but also has the potential to be fully integrated into patient screening and treatment monitoring of future NTR1 targeted therapies.

Synthesis and Evaluation of 64Cu-DOTA-NT-Cy5.5 as a Dual-Modality PET/Fluorescence Probe to Image Neurotensin Receptor-Positive Tumor.

Overexpression of neurotensin receptors (NTRs) has been suggested to play important roles in the growth and survival of a variety of tumor types. The aim of this study is to develop a dual-modality probe (64Cu -DOTA-NT-Cy5.5) for imaging NTR1 expression in vivo with both positron emission tomography (PET) and fluorescence. In this approach, the thiol group and N terminal amino group of neurotensin analogue (Cys-NT) were chemically modified with Cy5.5 dye and DOTA chelator, respectively. After radiolabeling with 64Cu, the resulting probe (64Cu-DOTA-NT-Cy5.5) was evaluated in NTR1 positive HT-29 tumor model. Small animal PET quantification analysis demonstrated that the tumor uptake was 1.91±0.22 and 1.79±0.16%ID/g at 1 and 4 h postinjection (p.i.), respectively. The tumor-to-muscle ratio was 17.44±3.25 at 4 h p.i. based on biodistribution. Receptor specificity was confirmed by the successful blocking experiment at 4 h p.i. (0.42±0.05%ID/g). In parallel with PET experiment, fluorescence imaging was also performed, which demonstrated prominent tumor uptake in HT-29 model. As a proof of concept, an imaging guided surgery was performed to the fluorescent moiety of this probe and could provide potential surgery guidance for NTR positive patients. In summary, our results clearly indicated that the dual-modality probe, 64Cu-DOTA-NT-Cy5.5, could serve as a promising agent to image NTR positive tumors in vivo.

PET Imaging of Dll4 Expression in Glioblastoma and Colorectal Cancer Xenografts Using (64)Cu-Labeled Monoclonal Antibody 61B.

Delta-like ligand 4 (Dll4) expressed in tumor cells plays a key role to promote tumor growth of numerous cancer types. Based on a novel antihuman Dll4 monoclonal antibody (61B), we developed a (64)Cu-labeled probe for positron emission tomography (PET) imaging of tumor Dll4 expression. In this study, 61B was conjugated with the (64)Cu-chelator DOTA through lysine on the antibody. Human IgG (hIgG)-DOTA, which did not bind to Dll4, was also prepared as a control. The Dll4 binding activity of the probes was evaluated through the bead-based binding assay with Dll4-alkaline phosphatase. The resulting PET probes were evaluated in U87MG glioblastoma and HT29 colorectal cancer xenografts in athymic nude mice. Our results demonstrated that the 61B-DOTA retained (77.2 ± 3.7) % Dll4 binding activity of the unmodified 61B, which is significantly higher than that of hIgG-DOTA (0.06 ± 0.03) %. Confocal microscopy analysis confirmed that 61B-Cy5.5, but not IgG-Cy5.5, predominantly located within the U87MG and HT29 cells cytoplasm. U87MG cells showed higher 61B-Cy5.5 binding as compared to HT29 cells. In U87MG xenografts, 61B-DOTA-(64)Cu demonstrated remarkable tumor accumulation (10.5 ± 1.7 and 10.2 ± 1.2%ID/g at 24 and 48 h postinjection, respectively). In HT29 xenografts, tumor accumulation of 61B-DOTA-(64)Cu was significantly lower than that of U87MG (7.3 ± 1.3 and 6.6 ± 1.3%ID/g at 24 and 48 h postinjection, respectively). The tumor accumulation of 61B-DOTA-(64)Cu was significantly higher than that of hIgG-DOTA-(64)Cu in both xenografts models. Immunofluorescence staining of the tumor tissues further confirmed that tumor accumulation of 61B-Cy5.5 was correlated well with in vivo PET imaging data using 61B-DOTA-(64)Cu. In conclusion, 61B-DOTA-(64)Cu PET probe was successfully synthesized and demonstrated prominent tumor uptake by targeting Dll4. 61B-DOTA-(64)Cu has great potential to be used for noninvasive Dll4 imaging, which could be valuable for tumor detection, Dll4 expression level evaluation, and Dll4-based treatment monitoring.

Manufacturing 6-[18F]Fluoro-L-DOPA via Flow Chemistry-Enhanced Photoredox Radiofluorination.

In this study, we introduce a practical methodology for the synthesis of PET probes by seamlessly combining flow chemistry with photoredox radiofluorination. The clinical PET tracer 6-[18F]FDOPA was smoothly prepared in a 24.3% non-decay-corrected yield with over 99.0% radiochemical purity (RCP) and enantiomeric excess (ee), notably by a simple cartridge-based purification. The flow chemistry-enhanced photolabeling method supplies an efficient and versatile solution for the synthesis of 6-[18F]FDOPA and for more PET tracer development.

Synthesis of 64Cu-, 55Co-, and 68Ga-Labeled Radiopharmaceuticals Targeting Neurotensin Receptor-1 for Theranostics: Adjusting In Vivo Distribution Using Multiamine Macrocycles.

The development of theranostic radiotracers relies on their binding to specific molecular markers of a particular disease and the use of corresponding radiopharmaceutical pairs thereafter. This study reports the use of multiamine macrocyclic moieties (MAs), as linkers or chelators, in tracers targeting the neurotensin receptor-1 (NTSR-1). The goal is to achieve elevated tumor uptake, minimal background interference, and prolonged tumor retention in NTSR-1-positive tumors. Methods: We synthesized a series of neurotensin antagonists bearing MA linkers and metal chelators. The MA unit is hypothesized to establish a strong interaction with the cell membrane, and the addition of a second chelator may enhance water solubility, consequently reducing liver uptake. Small-animal PET/CT imaging of [64Cu]Cu-DOTA-SR-3MA, [64Cu]Cu-NT-CB-NOTA, [68Ga]Ga-NT-CB-NOTA, [64Cu]Cu-NT-CB-DOTA, and [64Cu]Cu-NT-Sarcage was acquired at 1, 4, 24, and 48 h after injection using H1299 tumor models. [55Co]Co-NT-CB-NOTA was also tested in HT29 (high NTSR-1 expression) and Caco2 (low NTSR-1 expression) colorectal adenocarcinoma tumor models. Saturation binding assay and internalization of [55Co]Co-NT-CB-NOTA were used to test tracer specificity and internalization in HT29 cells. Results: In vivo PET imaging with [64Cu]Cu-NT-CB-NOTA, [68Ga]Ga-NT-CB-NOTA, and [55Co]Co-NT-CB-NOTA revealed high tumor uptake, high tumor-to-background contrast, and sustained tumor retention (≤48 h after injection) in NTSR-1-positive tumors. Tumor uptake of [64Cu]Cu-NT-CB-NOTA remained at 76.9% at 48 h after injection compared with uptake 1 h after injection in H1299 tumor models, and [55Co]Co-NT-CB-NOTA was retained at 60.2% at 24 h compared with uptake 1 h after injection in HT29 tumor models. [64Cu]Cu-NT-Sarcage also showed high tumor uptake with low background and high tumor retention 48 h after injection Conclusion: Tumor uptake and pharmacokinetic properties of NTSR-1-targeting radiopharmaceuticals were greatly improved when attached with different nitrogen-containing macrocyclic moieties. The study results suggest that NT-CB-NOTA labeled with either 64Cu/67Cu, 55Co/58mCo, or 68Ga (effect of 177Lu in tumor to be determined in future studies) and NT-Sarcage labeled with 64Cu/67Cu or 55Co/58mCo may be excellent diagnostic and therapeutic radiopharmaceuticals targeting NTSR-1-positive cancers. Also, the introduction of MA units to other ligands is warranted in future studies to test the generality of this approach.

Noninvasive positron emission tomography imaging of cell death using a novel small-molecule probe, (18)F labeled bis(zinc(II)-dipicolylamine) complex.

The synthetic bis(zinc(II)-dipicolylamine) (DPAZn2) coordination complexes are known to have a high specific and selective affinity to target the exposed phosphatidylserine (PS) on the surface of dead and dying cells. An (18)F-labeled DPAZn2 complex (4-(18)F-Fluoro-benzoyl-bis(zinc(II)-dipicolylamine), (18)F-FB-DPAZn2) as positron emission tomography (PET) tracer was developed and evaluated for in vivo imaging of tumor treated with a chemical agent. The in vitro cell stain studies revealed that fluorescent DPAZn2 complexes (Dansyl-DPAZn2) stained the same cells (apoptotic and necrotic cells) as fluorescein isothiocyanate (FITC) labeled Annexin V (FITC-Annexin V). The radiosynthesis of (18)F-FB-DPAZn2 was achieved through the amidation the precursor bis(2,2'-dipicolylamine) derivative (DPA2) with the prosthetic group N-succinimidyl-4-[(18)F]-fluorobenzoate ((18)F-SFB) and chelation with zinc nitrate. In the biodistribution study, the fast clearance of (18)F-FB-DPAZn2 from blood and kidney was observed and high uptake in liver and intestine within 90 min postinjection was also found. For the PET imaging, significantly higher tumor uptake of (18)F-FB-DPAZn2 was observed in the adriamycin (ADM)-treated Hepa1-6 hepatocellular carcinoma-bearing mice than that in the untreated tumor-model mice, while a slightly decreased tumor uptake of (18)F-FDG was found in the ADM-treated tumor-bearing mice. The results indicate that (18)F-FB-DPAZn2 has the similar capability of apoptosis detection as FITC-Annexin V and seems to be a potential PET tracer for noninvasive evaluation and monitoring of anti-tumor chemotherapy. The high uptake of (18)F-FB-DPAZn2 in the abdomen needs to optimize the structure for improving its pharmacokinetics characteristics in the future work.

Development of 18F-Labeled hydrophilic trans-cyclooctene as a bioorthogonal tool for PET probe construction.

We report the development of a hydrophilic 18F-labeled a-TCO derivative [18F]3 (log P = 0.28) through a readily available precursor and a single-step radiofluorination reaction (RCY up to 52%). We demonstrated that [18F]3 can be used to construct not only multiple small molecule/peptide-based PET agents, but protein/diabody-based imaging probes in parallel.

Comparative study on imaging and pathological features of elastofibroma dorsi.

BACKGROUND AND OBJECTIVE: Elastofibroma dorsi has an extremely low incidence. At present, comparative study on imaging manifestations and pathologic findings of elastofibroma dorsi has not been reported in China. This study was to investigate clinical manifestations, computed tomography (CT) and magnetic resonance imaging (MRI) appearances, and pathologic features of elastofibroma dorsi and to improve preoperative imaging diagnosis of this disease. METHODS: The clinical manifestations, imaging findings, and pathologic appearances of 6 cases of elastofibroma dorsi were retrospectively analyzed and related literatures were reviewed. All patients were examined with MRI, and 4 of them were examined with CT scan. RESULTS: All patients were above 30 years old without obvious symptoms. The tumors presented as a lenticular soft-tissue mass in the deep subscapular region. The tumor's density on plain CT scan or signal intensity on MR T1-weighted image was approximately equal to that of muscle with some interlaced fat-like areas within mass suppressed by fat-suppression MR sequences, which corresponded to dense collagen tissue and interspersed mature adipose tissue observed microscopically. CONCLUSIONS: CT and MRI can reflect the histological features of elastofibroma dorsi. On the basis of their imaging characteristics, a correct preoperative diagnosis of elastofibroma dorsi can easily be made.

Detection of salivary aspiration using radionuclide salivagram SPECT/CT in patients with COPD exacerbation: a preliminary study.

BACKGROUND: The aim of this prospective study was to assess the utility of radionuclide salivagram for detecting salivary aspiration in AECOPD patients and to evaluate the adding value of SPECT/CT to planar imaging. METHODS: 52 consecutive AECOPD patients underwent radionuclide salivagram SPECT/CT and water swallow test between April 2012 and March 2014. All images were interpreted independently by two experienced nuclear medicine physicians. Final diagnosis was made by consensus of two readers. The radionuclide salivagram and water swallow test results were compared using kappa values. The relationship between radionuclide salivagram results and exacerbation frequency was evaluated with the Person χ2 test. RESULTS: Salivary aspiration was diagnosed by radionuclide salivagram in 17 of 52 patients. Aspiration into the right main bronchus and branch was seen in 8 patients, bilateral main bronchi in 6 patients, and left lung field in 3 patients. SPECT/CT provided more accurate information on the extent and location of salivary aspiration, in 11 cases, SPECT/CT demonstrated aspiration of pulmonary segment bronchus and the following areas. Moreover, SPECT/CT revealed salivary aspiration corresponding to aspiration pneumonia in 8 cases. There was general agreement between the radionuclide salivagram and water swallow test results (Kappa =0.712; 95% CI, 0.504-0.920; P<0.001). The incidence of frequent exacerbations was greater among subjects with positive salivagram than among those with negative salivagram results (RR =3.43; 95% CI, 1.90-6.19; P<0.001). CONCLUSIONS: Radionuclide salivagram is an objective method for detecting salivary aspiration in AECOPD patients. Moreover, SPECT/CT can identify more precise location of salivary aspiration and suggest a possible role for saliva in the pathophysiology of aspiration pneumonia.

Matching Chelators to Radiometals for Positron Emission Tomography Imaging- Guided Targeted Drug Delivery.

Positron emission tomography (PET) is a functional imaging modality that measures pathophysiology status of disease noninvasively, and has become a key component for innovative drug delivery system (DDS) studies recently. The development of multifunctional chelating agents is critical for developing PET radiopharmaceuticals and therefore has become a hot and demanding research topic recently. The optimal chelators should be readily attached to biomolecules covalently, able to form stable complexes with radiometals, and demonstrate good bio-distribution pattern in vivo. Indeed, the selection of suitable chelators can facilitate the development of an effective PET imaging probe by improving targeting properties and providing favorable in vivo pharmacokinetics of radiolabeled probes. This review focuses on the recent developments of multifunctional chelators that are suitable for both imaging and radiation therapy.

Expression of protein TARBP1 in human hepatocellular carcinoma and its prognostic significance.

OBJECTIVE: The objective of this study was to analyze the expression of TARBP1 and its clinical significance in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: 90 patients with primary hepatocellular carcinoma were included in this study. The tumor and paired adjacent non-tumor tissues were collected. TARBP1 expression was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry. Associations of TARBP1 expression with the clinicopathological features were analyzed, and prognosis of HCC patients was evaluated. RESULTS: The result show the expression of TARBP1 mRNA in liver cancer tissues were higher than in the adjacent normal liver tissues in 10 paired samples (P=0.0015). Compared with adjacent normal liver tissues, overexpression of TARBP1 was detected in 61.1% (55/90) HCC patients. TARBP1 expression was associated with the AJCC tumor stage (P=0.004) and clinical stage (P=0.005), and decreased overall survival (P=0.002). In multivariate analysis, TARBP1 expression was an independent prognostic factor for overall survival (Hazard ratio [HR]=2.773, 95% confidence interval [CI] 1.542-4.985; P=0.019). CONCLUSIONS: TARBP1 is up-regulated in HCC, and the expression of TARBP1 was associated with the pathological grading and clinical stage. TARBP1 maybe is an independent prognostic marker of HCC patients.

Relapsing polychondritis on PET/CT.

Relapsing polychondritis is a rare multisystemic disease, which is characterized by recurrent inflammation of the cartilaginous structures. We report a case of a 37-year-old man with progressive respiratory distress. Chest Computed tomography (CT) demonstrated increased attenuation and smooth thickening of airway walls. Positron emission tomography/CT scan identified the multisystemic cartilaginous abnormalities that were recognized by an increased fluorine-18 deoxyglucose uptake on nasal cartilages, laryngeal cartilages, tracheobronchial tree, and rib cartilages. Positron emission tomography/CT is a useful tool to diagnose relapsing polychondritis, as the condition shows multisystemic cartilaginous abnormalities that can be identified by an increased fluorine-18 deoxyglucose uptake.

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

PURPOSE: C-Labeled 2-ß-carbomethoxy-3-ß-(4-fluorophenyl)tropane (C-CFT) is a commonly used positron emission tomography (PET) tracer for dopamine transporters imaging. The present study estimated human radiation absorbed doses of C-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 C-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 C-CFT associated with in this study are well within accepted limits. C-CFT demonstrates a favorable radiation dose profile in humans and allows multiple PET examinations on the same subject per year.

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

BACKGROUND AND AIM: [C]methyl iodide ([C]CH3I) is the most extensively used methylation agent for the preparation of a majority of C-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 [C]methyl bromide ([C]CH3Br) as an analog of [C]CH3I is derived by the wet method in this study. Radiosynthesis of L-[S-methyl-C]methionine (MET), L-[S-methyl-C]cysteine (MCYS), [N-methyl-C]choline (CH), [C]methyl triflate ([C]CH3OSO2CF3), and [C]-2-ß-carbomethoxy-3-ß-(4-fluorophenyl)-tropane (CFT) by methylation reaction with [C]CH3Br, and PET imaging of patients are also described. METHODS: The preparation of [C]CH3Br by a one-pot wet method involved the following steps: reduction of [C]carbon dioxide with lithium aluminium hydride (LiAlH4) solution, treatment with hydrobromic acid, and distillation of [C]CH3Br under continuous nitrogen flow. [C]methylation of L-homocysteine thiolactone hydrochloride, L-cysteine, 2-dimethylaminoethanol, silver triflate, and nor-ß-CFT as precursors with [C]CH3Br and purification with Sep-Pak cartridges gave MET, MCYS, CH, [C]CH3OSO2CF3, and CFT, respectively. In addition, PET imaging of brain cancer and Parkinson's disease was carried out. RESULTS: The uncorrected radiochemical yield of [C]CH3Br was (37.8±2.5%) based on [C]carbon dioxide within a total synthesis time of 10 min and the radiochemical purity of [C]CH3Br was greater than 95%. The uncorrected yields of MET, MCYS, CH, [C]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 [C]CH3OSO2CF3) within a total synthesis time of 2, 2, 5, 1, and 8 min, respectively. The radiochemical purity of MET, MCYS, CH, [C]CH3OSO2CF3, and CFT was more than 95%. Good PET images in the patients are obtained. CONCLUSION: Automated synthesis of [C]CH3Br can be done by the wet method on the commercial [C]CH3I synthesizer. [C]CH3Br can be used for a [C]methylation reaction to produce C-labeled tracers for clinical PET imaging.

S-11C-methyl-L-cysteine: a new amino acid PET tracer for cancer imaging.

UNLABELLED: S-(11)C-methyl-L-cysteine ((11)C-MCYS), an analog of S-(11)C-methyl-L-methionine ((11)C-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 (11)C-MCYS as a tumor imaging tracer. The results of the first human PET study are reported. METHODS: (11)C-MCYS was prepared by (11)C-methylation of the precursor L-cysteine with (11)CH(3)I and purification on commercial C18 cartridges. In vitro competitive inhibition experiments were performed with Hepa1-6 hepatoma cell lines, and biodistribution of (11)C-MCYS was determined in normal mice. The incorporation of (11)C-MCYS into tissue proteins was investigated. In vivo (11)C-MCYS uptake studies were performed on hepatocellular carcinoma-bearing nude mice and inflammation models and compared with (11)C-MET PET and (18)F-FDG PET. In a human PET study, a patient with a recurrence of glioma after surgery was examined with (11)C-MCYS PET and (18)F-FDG PET. RESULTS: The uncorrected radiochemical yield of (11)C-MCYS from (11)CH(3)I was more than 50% with a synthesis time of 2 min, the radiochemical purity of (11)C-MCYS was more than 99%, and the enantiomeric purity was more than 90%. In vitro studies showed that (11)C-MCYS transport was mediated through transport system L. Biodistribution studies demonstrated high uptake of (11)C-MCYS in the liver, stomach wall, and heart and low uptake of (11)C-MCYS in the brain. There was higher accumulation of (11)C-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 (11)C-MCYS, 5.08 and 3.88, respectively, for (18)F-FDG, and 4.26 and 2.28, respectively, for (11)C-MET at 60 min after injection. Almost no (11)C-MCYS was incorporated into proteins. For the patient PET study, high uptake of (11)C-MCYS with true-positive results, but low uptake of (18)F-FDG with false-negative results, was found in the recurrent glioma. CONCLUSION: Automated synthesis of (11)C-MCYS is easy to perform. (11)C-MCYS is superior to (11)C-MET and (18)F-FDG in the differentiation of tumor from inflammation and seems to have potential as an oncologic PET tracer for the diagnosis of solid tumors.