Caihua Tang

Radiosynthesis and preliminary biological evaluation of N-(2- [ 18 F]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.

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.

18F-FP-PEG2-β-Glu-RGD2: A Symmetric Integrin αvβ3-Targeting Radiotracer for Tumor PET Imaging

Radiolabeled cyclic arginine-glycine-aspartic (RGD) peptides can be used for noninvasive determination of integrin αvβ3 expression in tumors. In this study, we performed radiosynthesis and biological evaluation of a new 18F-labeled RGD homodimeric peptide with one 8-amino-3,6-dioxaoctanoic acid (PEG2) linker on the glutamate β-amino group (18F-FP-PEG2-β-Glu-RGD2) as a symmetric PET tracer for tumor imaging. Biodistribution studies showed that radioactivity of 18F-FP-PEG2-β-Glu-RGD2 was rapidly cleared from blood by predominately renal excretion. MicroPET-CT imaging with 18F-FP-PEG2-β-Glu-RGD2 revealed high tumor contrast and low background in A549 human lung adenocarcinoma-bearing mouse models, PC-3 prostate cancer-bearing mouse models, and orthotopic transplanted C6 brain glioma models. 18F-FP-PEG2-β-Glu-RGD2 exhibited good stability in vitro and in vivo. The results suggest that this tracer is a potential PET tracer for tumor imaging.

Molecular PET Imaging of Cyclophosphamide Induced Apoptosis with 18F-ML-8

In this paper, a novel small-molecular apoptotic PET imaging probe, 18F-ML-8 with a malonate motif structure, is presented and discussed. After study, the small tracer that belongs to a member of ApoSense family is proved to be capable of imaging merely apoptotic regions in the CTX treated tumor-bearing mice. The experimental result is further confirmed by in vitro cell binding assays and TUNEL staining assay. As a result, 18F-ML-8 could be used for noninvasive visualization of apoptosis induced by antitumor chemotherapy.

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.

Radiation dosimetry estimation of N-(2-[18F]fluoropropionyl)- l-glutamate based on the mice distribution data

N-(2-[(18)F]fluoropropionyl)-l-glutamate([(18)F]FPGLU) was a recently developed potential amino acid tracer for tumor imaging with positron emission tomography-computer tomography (PET-CT). The absorbed and effective radiation doses resulting from the intravenous administration of [(18)F]FPGLU were estimated using biodistribution data from normal mice. The methodology recommended by Medical Internal Radiation Dose Committee (MIRD) was used to estimate the doses. The highest uptake of [(18)F]FPGLU was found in the kidneys, followed by the liver and lung. The kidneys were the organ received the highest absorbed dose, 58.4μGy/MBq, the brain received the lowest dose, 5.5μGy/MBq, and other organs received doses in the range of 8.3-11.9μGy/MBq. The effective dose was 17.0μSv/MBq. The data show that a 370MBq (10mCi) injection of [(18)F]FPGLU would lead to an estimated effective dose of 6.3mSv, which is within the accepted range of routine nuclear medicine investigations.