Radiosynthesis of novel N-18 F-labeled 18 F-FHex-α-l-Glu and 18 F-FHex-ß-Glu.

N-18 F-labeled amino acids are important substitutes for new positron emission tomography (PET) imaging tracers complementing the deficiency of 18 F-fluorodeoxyglucose (18 F-FDG). In this work, two novel N-6-18 F-alkyl amino acid imaging agents, 18 F-FHex-α-l-Glu and 18 F-FHex-ß-Glu, were designed and synthesized as potential probes for PET imaging of tumors. 18 F-FHex-α-l-Glu was synthesized using the precursor 6 from 18 F-F- with the yield of 16 ± 4% (n = 5, uncorrected) within about 50 minutes. The specific activity was 14.5 GBq/µmol, and the radiochemical purity was more than 95%. 18 F-FHex-ß-Glu was synthesized using the precursor 12 based on 18 F-F- with the yield of 11 ± 3% (n = 3, uncorrected) in about 60 minutes. The specific activity was 9.1 GBq/µmol, and the radiochemical purity was more than 95%.

Semi-automatic synthesis and biodistribution of N-(2-18F-fluoropropionyl)-bis(zinc (II)-dipicolylamine) (18F-FP-DPAZn2) for AD model imaging.

BACKGROUND: Phosphatidylserine (PS)-targeting positron emission tomography (PET) imaging with labeled small-molecule tracer is a crucial non-invasive molecule imaging method of apoptosis. In this study, semi-automatic radiosynthesis and biodistribution of N-(2-18F-fluoropropionyl)-bis(zinc(II)-dipicolylamine) (18F-FP-DPAZn2), as a potential small-molecule tracer for PET imaging of cell death in Alzheimer's disease (AD) model, were performed. METHODS: 18F-FP-DPAZn2 was synthesized on the modified PET-MF-2V-IT-I synthesizer. Biodistribution was determined in normal mice and PET images of AD model were obtained on a micro PET-CT scanner. RESULTS: With the modified synthesizer, the total decay-corrected radiochemical yield of 18F-FP-DPAZn2 was 35 ± 6% (n = 5) from 18F- within 105 ± 10 min. Biodistribution results showed that kidney has the highest uptake of 18F-FP-DPAZn2. The uptake of radioactivity in brain kept at a relatively low level during the whole observed time. In vivo 18F-FP-DPAZn2 PET images demonstrated more accumulation of radioactivity in the brain of AD model mice than that in the brain of normal mice. CONCLUSIONS: The semi-automatic synthetic method provides a slightly higher radiochemical yield and shorter whole synthesis time of 18F-FP-DPAZn2 than the manual operation method. This improved method can give enough radioactivity and high radiochemical purity of 18F-FP-DPAZn2 for in vivo PET imaging. The results show that 18F-FP-DPAZn2 seems to be a potential cell death tracer for AD imaging.

Optimization and automation of the radiosynthesis of [18F]Lu-LuFL as a clinically useful PET ligand targeting FAP for tumor imaging.

Recently, a novel radiohybrid tracer [18F]Lu-LuFL targeting the fibroblast activation protein (FAP) has been developed for PET imaging of solid tumors. This tracer has shown promising results, prompting us to conduct a first-in-human study to evaluate its efficacy for PET imaging of FAP in human body. In order to facilitate the routine production and clinical application of [18F]Lu-LuFL, a straightforward and efficient automated synthesis is described. The optimum labeling parameters were determined at laboratory scale, and subsequently incorporated into an automated production process. Further studies have demonstrated that clinical doses of [18F]Lu-LuFL can be prepared within 19 min, with excellent radio chemical purity (>99%) and activity yield (23.58% ± 2.20%, non-decay corrected), coupled with solid phase extraction (SPE) purification method. All the quality control results satisfy the required criteria for release. In conclusion, we have successfully synthesized [18F]Lu-LuFL with sufficient radioactivity and superior quality, thereby establishing its potential for further clinical application.

Effects of STN-DBS surgery on cerebral glucose metabolism and distribution of DAT in Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder that affects millions of people worldwide. Subthalamic nucleus (STN) deep brain stimulation (DBS) has been shown to be an effective treatment for PD; however, the effects of this surgery on cerebral metabolism and presynaptic dopamine transporter (DAT) distribution are still being studied. METHODS: In this study, we included 12 PD patients (6 male and 6 female) who underwent STN-DBS surgery and had both 18 F-FDG and 11 C-CFT PET/CT imaging before and 1 year after the surgery. We used paired t-tests to identify changes in cerebral metabolism and calculated PD-related metabolic covariance pattern (PDRP) scores. We also assessed the uptake of 11 C-CFT in the striatum using striatal-to-occipital ratios (SORs). RESULTS: One year after surgery, we observed significant reductions in tremor, rigidity, akinesia, postural instability/gait disturbance, and Unified Parkinson's Disease Rating Scale Part III scores (p < .01, p < .001, p < .001, p < .001, and p < .001, respectively). Hamilton Depression Rating Scale and quality of life (PDQ-39 SI) were also significantly reduced (p < .05 and p < .01, respectively). The mean PDRP score decreased by 37% from 13.0 ± 6.6 to 8.2 ± 7.9 after STN-DBS surgery (p < .05). We observed decreased 18 F-FDG uptake in several areas, including the temporal lobe (BA22), thalamus, putamen, and cingulate gyrus (BA24), whereas it was increased in the supplementary motor area, postcentral gyrus, lingual gyrus, and precuneus (p < .05). SORs of 11 C-CFT in the bilateral caudate nucleus and ipsilateral posterior putamen were significantly decreased compared to preoperative levels (p < .05). CONCLUSION: Our findings suggest that STN-DBS surgery modifies the metabolic network of PD patients and improves motor symptoms, depression, and quality of life. However, it does not prevent the decrease of DAT in striatal areas.

18F-Trifluoromethylated D-Cysteine as a Promising New PET Tracer for Glioma Imaging: Comparative Analysis With MRI and Histopathology in Orthotopic C6 Models.

Comparing MRI and histopathology, this study aims to comprehensively explore the potential application of 18F-trifluoromethylated D-cysteine (S-[18F]CF3-D-CYS) in evaluating glioma by using orthotopic C6 glioma models. Sprague-Dawley (SD) rats (n = 9) were implanted with C6 glioma cells. Tumor growth was monitored every week by multiparameter MRI [including dynamic contrast-enhanced MRI (DCE-MRI)], [18F]FDG, S-[18F]CF3-D-CYS, and [18F]FDOPA PET imaging. Repeated scans of the same rat with the two or three [18F]-labeled radiotracers were investigated. Initial regions of interest were manually delineated on T2WI and set on the same level of PET images, and tumor-to-normal brain uptake ratios (TNRs) were calculated to semiquantitatively assess the tracer accumulation in the tumor. The tumor volume in PET and histopathology was calculated. HE and Ki67 immunohistochemical staining were further performed. The correlations between the uptake of S-[18F]CF3-D-CYS and Ki67 were analyzed. Dynamic S-[18F]CF3-D-CYS PET imaging showed tumor uptake rapidly reached a peak, maintained plateau during 10-30 min after injection, then decreased slowly. Compared with [18F]FDG and [18F]FDOPA PET imaging, S-[18F]CF3-D-CYS PET demonstrated the highest TNRs (P < 0.05). There were no significant differences in the tumor volume measured on S-[18F]CF3-D-CYS PET or HE specimen. Furthermore, our results showed that the uptake of S-[18F]CF3-D-CYS was significantly positively correlated with tumor Ki67, and the poor accumulated S-[18F]CF3-D-CYS was consistent with tumor hemorrhage. There was no significant correlation between the S-[18F]CF3-D-CYS uptakes and the Ktrans values derived from DCE-MRI. In comparison with MRI and histopathology, S-[18F]CF3-D-CYS PET performs well in the diagnosis and evaluation of glioma. S-[18F]CF3-D-CYS PET may serve as a valuable tool in the clinical management of gliomas.

Excitatory glutamate transporter EAAC1 as an important transporter of N-(2-[18F]fluoropropionyl)-L-glutamate in oncology PET imaging.

INTRODUCTION: We have reported that N-(2-[18F]fluoropropionyl)-L-glutamate ([18F]FPGLU) was a potential amino acid tracer for tumor imaging with positron emission tomography (PET). In this study, the relationship between glutamate transporter excitatory amino acid carrier 1 (EAAC1) expression and [18F]FPGLU uptake in rat C6 glioma cell lines and human SPC-A-1 lung adenocarcinoma cell lines was investigated. METHODS: The uptake of [18F]FPGLU was assessed in ATRA-treated and untreated C6 cell lines, and also in EAAC1 knock-down SPC-A-1(shRNA) cells and SPC-A-1(NT) control cells. PET imaging of [18F]FPGLU was performed on the SPC-A-1 and SPC-A-1 (shRNA)-bearing mice models. RESULTS: The uptake of [18F]FPGLU in C6 cells increased significantly after induced by ATRA for 24, 48, and 72 h, which was closely related to expression of EAAC1 in C6 cells (R2 = 0.939). Compared with the SPC-A-1(NT) control cells, the uptake of [18F]FPGLU on EAAC1 knock-down SPC-A-1(shRNA) cells significantly decreased to 64.0%. Moreover, the uptake of [18F]FPGLU in EAAC1 knock-down SPC-A-1(shRNA) xenografts was significantly lower than that in SPC-A-1 xenografts, with tumor/muscle ratios of 3.01 vs. 1.67 at 60 min post-injection of [18F]FPGLU. CONCLUSION: The transport mechanism of [18F]FPGLU in glioma C6 and lung adenocarcinoma SPC-A-1 cell lines mainly involves in glutamate transporter EAAC1. EAAC1 is an important transporter of N-(2-[18F]fluoropropionyl)-L-glutamate in oncologic PET imaging.

Targeting Phosphatidylethanolamine with Fluorine-18 Labeled Small Molecule Probe for Apoptosis Imaging.

PURPOSE: Externalization of phosphatidylethanolamine (PE) in dying cells makes the phospholipid an attractive target for apoptosis imaging. However, no ideal PE-targeted positron emission tomography (PET) radiotracer was developed. The goal of the study was to develop a novel PE-targeted radiopharmaceutical to imaging apoptosis. PROCEDURE: In this study, we have radiolabeled PE-binding polypeptide duramycin with fluorine-18 for PET imaging of apoptosis. Al[18F]F-NOTA-PEG3-duramycin was synthesized via chelation reaction of NOTA-PEG3-duramycin with Al[18F]F. PE-binding capacity of Al[18F]F-NOTA-PEG3-duramycin was determined in a competitive radiometric PE-binding assay. The pharmacokinetic profile was evaluated in Kunming mice. The apoptosis imaging capacity of Al[18F]F-NOTA-PEG3-duramycin was evaluated using in vitro cell uptake assay with camptothecin-treated Jurkat cells, along with in vivo PET imaging using erlotinib-treated nude mice. RESULTS: The total synthesis procedure lasted for 30 min, with a decay-uncorrected radiochemical yield of 21.3 ± 2.6 % (n = 10). Compared with the control cells, the binding of Al[18F]F-NOTA-PEG3-duramycin with camptothecin-induced apoptotic cells resulted in a tripling increase. A competitive radiometric PE-binding assay strongly confirmed the binding of Al[18F]F-NOTA-PEG3-duramycin to PE. The biodistribution study showed rapid blood clearance, prominent kidney retention, and low liver uptake. In the in vivo PET/CT imaging, Al[18F]F-NOTA-PEG3-duramycin demonstrated 2-fold increase in erlotinib-treated HCC827 tumors in nude mice. CONCLUSION: Considering the facile preparation and improved biological properties, Al[18F]F-NOTA-PEG3-duramycin seems to be a promising PET tracer candidate for imaging apoptosis in the monitoring of cancer treatment.

Validation of R-2-[18F]Fluoropropionic Acid as a Potential Tracer for PET Imaging of Liver Cancer.

PURPOSE: 2-[18F]Fluoropropionic acid (RS-[18F]FPA) has shown potential value as a short-chain fatty acid positron emission tomography (PET) tracer for the detection of liver cancer. However, RS-[18F]FPA is a mixture of 2-R-[18F]fluoropropionic acid (R-[18F]FPA) and 2-S-[18F]fluoropropionic acid (S-[18F]FPA). The aim of this study is to validate the feasibility of R-[18F]FPA in preclinical PET imaging of liver cancer and to compare the use of R-[18F]FPA with that of RS-[18F]FPA and S-[18F]FPA. PROCEDURES: A comparative study of R-[18F]FPA, RS-[18F]FPA, S-[18F]FPA, and [18F]FDG micro-PET imaging was performed in HepG2 and SK-Hep-1 tumor-bearing mice. A comparison of R-[18F]FPA uptake with that of S-[18F]FPA by HepG2 and SK-Hep-1 cells was made at different time points. Additionally, in vivo blocking experiments in HepG2 and SK-Hep-1 tumor models were conducted with orlistat and 3-nitropropionic acid (3-NP). In vitro blocking experiments with orlistat or 3-NP were performed with HepG2 and SK-Hep-1 cells. RESULTS: The radioactivity uptake values of R-[18F]FPA were comparable to those of RS-[18F]FPA but were higher than those of S-[18F]FPA and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in HepG2 tumors. The radioactivity uptake values of R-[18F]FPA in large HepG2 tumors were lower than those of [18F]FDG (P < 0.05), while R-[18F]FPA PET was significantly superior to [18F]FDG PET in detecting small tumors (both SK-Hep-1 and HepG2 tumors). The in vivo PET imaging experiments showed that R-[18F]FPA uptake in HepG2 tumor-bearing mice was blocked by 19.3 % and 31.8 % after treatment with orlistat and 3-NP, respectively. The radioactivity uptake values of R-[18F]FPA in SK-Hep-1 tumor-bearing mice was blocked by 39.5 % with orlistat. CONCLUSION: R-[18F]FPA seems to be more potential than S-[18F]FPA as an optically pure PET probe, with effective compensation for the deficiencies of [18F]FDG, particularly in PET imaging of small liver cancer. The uptake mechanism of [18F]FPA in liver cancer may be related to fatty acid synthesis and the tricarboxylic acid cycle. However, compared with the racemic RS-[18F]FPA, the possible advantages of R-enantiomer R-[18F]FPA still needs further research.

Radiosynthesis and biological evaluation of N-(2-[18F]fluoropropionyl)-3,4-dihydroxy-l-phenylalanine as a PET tracer for oncologic imaging.

INTRODUCTION: Several 11C and 18F labeled 3,4-dihydroxy-l-phenylalanine (l-DOPA) analogues have been used for neurologic and oncologic diseases, especially for brain tumors and neuroendocrine tumors PET imaging. However, 18F-labeled N-substituted l-DOPA analogues have not been reported so far. In the current study, radiosynthesis and biological evaluation of a new 18F-labeled l-DOPA analogue, N-(2-[18F]fluoropropionyl)-3,4-dihydroxy-l-phenylalanine ([18F]FPDOPA) for tumor PET imaging are performed. METHODS: The synthesis of [18F]FPDOPA was via a two-step reaction sequence from 4-nitrophenyl-2-[18F]fluoropropionate ([18F]NFP). The biodistribution of [18F]FPDOPA was determined in normal Kunming mice. In vitro competitive inhibition and protein incorporation experiments were performed with SPC-A-1 lung adenocarcinoma cell lines. PET/CT studies of [18F]FPDOPA were conducted in C6 rat glioma and SPC-A-1 human lung adenocarcinoma and H460 human large cell lung cancer-bearing nude mice. RESULTS: [18F]FPDOPA was prepared with a decay-corrected radiochemical yield of 28±5% and a specific activity of 50±15GBq/µmol (n=10) within 125min. In vitro cell experiments showed that [18F]FPDOPA uptake in SPC-A-1 cells was primarily transported through Na+-independent system L, with Na+-dependent system B0,+ and system ASC partly involved in it. Biodistribution data in mice showed that renal-bladder route was the main excretory system of [18F]FPDOPA. PET imaging demonstrated intense accumulation of [18F]FPDOPA in several tumor xenografts, with (8.50±0.40)%ID/g in C6 glioma, (6.30±0.12)%ID/g in SPC-A-1 lung adenocarcinoma, and (6.50±0.10)%ID/g in H460 large cell lung cancer, respectively. CONCLUSION: A novel N-substituted 18F-labeled L-DOPA analogue [18F]FPDOPA is synthesized and evaluated in vitro and in vivo. The results support that [18F]FPDOPA seems to be a potential PET tracer for tumor imaging, especially be a better potential PET tracer than [18F]fluoro-2-deoxy-d-glucose ([18F]FDG) for brain tumor imaging.

Simple and rapid radiosynthesis of N-18F-labeled glutamic acid as a hepatocellular carcinoma PET tracer.

INTRODUCTION: We have reported that N-(2-18F-fluoropropionyl)-L-glutamate (18F-FPGLU) showed good tumor-to-background contrast and 18F-FPGLU was prepared via complex multi-step reaction sequence; here, it is synthesized by a facile two-step reaction sequence. The objectives of this study are to synthesize 18F-FPGLU via a two-step reaction sequence and to evaluate the value of 18F-FPGLU in nude mice bearing human hepatocellular carcinoma SMCC-7721 (HCC SMCC-7721). METHODS: 18F-FPGLU was synthetized from the precursor (2S)-dimethyl 2-(2-bromopropanamido)pentanedioate via the two-step on-column hydrolysis using a modified commercial FDG synthesizer. To investigate the transport mechanism of 18F-FPGLU, we conducted a series of competitive inhibition experiments on HCC SMCC-7721 cells in the absence or presence of Na+ and various types of inhibitors. Small-animal PET-CT imaging was performed on tumor-bearing nude mice using 18F-FPGLU and 2-18F-2-deoxy-D-glucose (18F-FDG). RESULTS: The radiochemical yield of 18F-FPGLU was up to 15±5% (EOS, n=10) in 35min with the two-step procedure and the radiochemical purity was higher than 95% with a specific activity of 30-40GBq/µmol. In vitro cell experiments show that 18F-FPGLU is primarily transported through the Na+-dependent system XAG- and Na+-independent system XC-. PET imaging in a tumor model indicates that 18F-FPGLU may be superior to 18F-FDG for hepatocellular carcinoma (HCC) imaging. CONCLUSION: An optimized route to prepare 18F-FPGLU was developed and 18F-FPGLU was synthetized from the precursor ((2S)-dimethyl 2-(2-bromopropanamido)pentanedioate) via the two-step on-column hydrolysis. 18F-FPGLU was a potential novel PET tracer for HCC imaging.

Radiosynthesis and preliminary biological evaluation of N-(2-[18F]fluoropropionyl)-L-glutamine as a PET tracer for tumor imaging.

In this study, radiosynthesis and biological evaluation of a new [18F]labeled glutamine analogue, N-(2-[18F]fluoropropionyl)-L-glutamine ([18F]FPGLN) for tumor PET imaging are performed. [18F]FPGLN was synthesized via a two-step reaction sequence from 4-nitrophenyl-2-[18F]fluoropropionate ([18F]NFP) with a decay-corrected yield of 30 ± 5% (n=10) and a specific activity of 48 ± 10 GBq/µmol after 125 ± 5 min of radiosynthesis. The biodistribution of [18F]FPGLN was determined in normal Kunming mice and high uptake of [18F]FPGLN was observed within the kidneys and quickly excreted through the urinary bladder. In vitro cell experiments showed that [18F]FPGLN was primarily transported by Na+-dependent system XAG- and was not incorporated into proteins. [18F]FPGLN displayed better stability in vitro than that in vivo. PET/CT studies revealed that intense accumulation of [18F]FPGLN were shown in human SPC-A-1 lung adenocarcinoma and PC-3 prostate cancer xenografts. The results support that [18F]FPGLN seems to be a possible PET tracer for tumor imaging.

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.

A facile and rapid automated synthesis of 3'-deoxy-3'-[(18)F]fluorothymidine.

AIM: To develop a simplified and fully automated synthesis procedure of 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) using PET-MF-2V-IT-I synthesis module. METHODS: Synthesis of [(18)F]FLT was performed using PET-MF-2V-IT-I synthesis module by one-pot two-step reaction procedure, including nucleophilic fluorination of 3-N-t-butoxycarbonyl-1-[5'-O-(4,4'-dimethoxy triphenylmethyl)-2'-deoxy-3'-O-(4-nitrobenzenesulfonyl)-beta-d-threopentofuranosyl]thymine (15mg) as the precursor molecule with [(18)F]fluoride, and subsequent hydrolysis of the protecting group with 1.0M HCl at the same reaction vessel and purification with SEP PAK cartridges instead of the HPLC system. RESULTS: The automated synthesis of [(18)F]FLT with SEP PAK purification gave corrected radiochemical yield of 23.2+/-2.6% (n=6, uncorrected yield: 16-22%) and radiochemical purity of >97% within the total synthesis time of 35min. CONCLUSION: The fully one-pot automated synthesis procedure with SEP PAK purification can be applied to the fully automated synthesis of [(18)F]FLT using commercial [(18)F]FDG synthesis module.