Homodimeric peptide radiotracer [68Ga]Ga-NOTA-(TMVP1)2 for VEGFR-3 imaging of cervical cancer patients.

PURPOSE: Vascular endothelial growth factor receptor 3 (VEGFR-3) plays a critical role in tumor lymphangiogenesis and metastasis, holding promise as a promising therapeutic target for solid tumors. TMVP1 (LARGR) is a 5-amino acid peptide previously identified in our laboratory from bacterial peptide display system that specifically targets VEGFR-3. Radiolabeled TMVP1 can be used for non-invasive imaging of VEGFR-3 expressing tumors. Homodimeric peptides have better targeting ability than monomeric peptides, and it is worth exploring whether homodimers of TMVP1 ((TMVP1)2) can achieve better imaging effects. This study aimed to explore the peptide properties and tumor assessment value of [68Ga]Ga-labeled (TMVP1)2. METHODS: In this study, we developed a TMVP1 homodimer that was conjugated with 1,4,7-triazacyclononane-N, N', N″-triacetic acid (NOTA) via tetraethyleneglycol (PEG4) and triglyicine (Gly3) spacer, and labeled with 68Ga, to construct [68Ga]Ga-NOTA-(TMVP1)2. Binding of VEGFR-3 by TMVP1 and (TMVP1)2, respectively, was modeled by molecular docking. The affinity of [68Ga]Ga-NOTA-(TMVP1)2 for VEGFR-3 and its ability to bind to cells were evaluated. MicroPET imaging and biodistribution studies of [68Ga]Ga-NOTA-(TMVP1)2 were performed in subcutaneous C33A cervical cancer xenografts. Five healthy volunteers and eight patients with cervical cancer underwent whole-body PET/CT acquisition 30-45 min after intravenous injection of [68Ga]Ga-NOTA-(TMVP1)2. RESULTS: Both molecular docking and cellular experiments showed that homodimeric TMVP1 had a higher affinity for VEGFR-3 than monomeric TMVP1. [68Ga]Ga-NOTA-(TMVP1)2 was excreted mainly through the renal route and partly through the liver route. In mice bearing C33A xenografts, [68Ga]Ga-NOTA-(TMVP1)2 specifically localized in the tumor (2.32 ± 0.10% ID/g). Pretreatment of C33A xenograft mice with the unlabeled peptide NOTA-(TMVP1)2 reduced the enrichment of [68Ga]Ga-NOTA-(TMVP1)2 in tumors (0.58 ± 0.01% ID/g). [68Ga]Ga-NOTA-(TMVP1)2 proved to be safe in all healthy volunteers and recruited patients, with no side effects or allergies noted. In cervical cancer patients, a majority of the [18F]-FDG identified lesions (18/22, 81.8%) showed moderate to high signal intensity on [68Ga]Ga-NOTA-(TMVP1)2. SUVmax and SUVmean were 2.32 ± 0.77 and 1.61 ± 0.48, respectively. With normal muscle (gluteus maximus) as background, tumor-to-background ratios were 3.49 ± 1.32 and 3.95 ± 1.64 based on SUVmax and SUVmean, respectively. CONCLUSION: The favorable characterizations of [68Ga]Ga-NOTA-(TMVP1)2 such as convenient synthesis, high specific activity, and high tumor uptake enable the evaluation of VEGFR-3 in cervical cancer patients and warrant further clinical studies. TRIAL REGISTRATION: ChiCTR-DOD-17012458. Registered August 23, 2017 (retrospectively registered).

Characterization of myocardial oxidative metabolism and myocardial external efficiency in high-risk alcohol cardiotoxicity and alcoholic cardiomyopathy via dynamic 11C-Acetate positron emission tomography.

INTRODUCTION: The purpose of this study was to evaluate subjects with high-risk alcohol cardiotoxicity and patients with alcoholic cardiomyopathy (ACM) via dynamic 11C-Acetate positron emission tomography (PET) imaging as a myocardial oxidative metabolic probe. METHODS AND RESULTS: We recruited 37 subjects with chronic alcohol consumption [18 with moderate consumption (MC), 19 with heavy consumption (HC)], 5 ACM patients, and 12 healthy controls to receive dynamic 11C-Acetate PET scans. PET imaging data were analyzed to calculate kinetic parameters (e.g., Kmono, K1 and k2) based on the mono-exponential and one-tissue compartmental models. Myocardial oxygen consumption (MVO2) and myocardial external efficiency (MEE) were then derived from these kinetic parameters. MVO2 was significantly lowered in the HC group and in ACM patients (0.121± 0.018 and 0.111 ± 0.017 mL·g-1·min-1, respectively) compared with those in healthy controls and MC subjects (0.144 ± 0.023 and 0.146 ± 0.027 mL·g-1·min-1, respectively; P < .01). MEE was significantly reduced in ACM patients (13.0% ± 4.3%) compared with those of healthy controls (22.4% ± 4.6%, P < .01), MC subjects (20.1% ± 4.5%, P < .05), and HC subjects (22.3% ± 4.5%, P < .001). CONCLUSION: Functional assessment via dynamic 11C-Acetate PET imaging may represent a clinically feasible probe for identifying cohorts with high-risk cardiotoxicity due to addictive alcohol consumption and ACM.

Imaging Potential and Biodistribution in vivo of 2-[18F]Fluoropropionic Acid in Breast Cancer-bearing Mice.

OBJECTIVE: To investigate the imaging potential and biodistribution in vivo of a novel positron imaging agent,2-[(18)F]fluoropropionic,in breast cancer-bearing mice. Methods: 2-[(18)F]fluoropropionic acid (7.4-11.1 MBq)was injected into the breast cancer-bearing mice via tail vein,followed by micro positron emission tomography at 60 min and 120 min.The radioactivity per volume (Bq/ml) in organs was transferred to percentage injected dose per gram(% ID/g)by Inveon Research software and the biodistribution of 2-[(18)F]fluoropropionic acid in organs was deduce.The same operations were done with (18)F-FDG. RESULTS: 2-[(18)F]fluoropropionic acid was mainly distributed in the urinary bladder,intestine,and liver between 60 min to 120 min.The breast cancer at right flank was visualized clearly,and the radioactivity uptake was (13.74±1.97)% ID/g and (14.84±1.06)% ID/g,respectively,at these two time points (P=0.454).The radioactivity uptakes in muscle and brown tissue were relatively low.The radioactivity uptake of (18)F-FDG was (10.27±2.34)% ID/g at the breast cancer 60 min after injection,and radioactivity uptake of the brown fat on the back was obvious. CONCLUSIONS: Positron imaging agent 2-[(18)F]fluoropropionic acid can be used to image breast cancer.It may be applied in the noninvasive imaging of breast cancer in clinical settings.

[Comparison analysis of multi-modalities images in 158 patients with hepatic tumor].

OBJECTIVE: To compare and analyze the positron emission tomography (PET) images with other multi-modalities in the diagnosis of hepatic tumors. METHODS: A total of 158 patients undergoing (18)F fluorodeoxyglucose (FDG)-PET were enrolled along with another 55 cases with (11)C acetate-PET (AC-PET) imaging within 1 week. The pathological results were taken as the golden criteria. Tumor marker, contrast ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) results were collected.SPSS 19.0 was used for statistical analysis. RESULTS: Contrast MRI, ultrasound and CT were more effective than PET in the differential diagnosis of hepatic tumor.FDG-PET showed a better accuracy in the diagnosis of intrahepatic cholangiocarcinomas, metastasis and rare primary hepatic carcinoma. AC-PET was a good complementary method to FDG-PET. Consideration of tumor size, amount, laboratory results and history could improve the diagnostic accuracy of PET and enhanced CT. CONCLUSION: PET must be combined with other image modalities to differentiate hepatic tumors more effectively and accurately.

[Expression and affinity purification of recombinant human epidermal growth factor receptor-2 affibody with C-terminal cystein].

OBJECTIVE: To prepare the modified ZHER2V2 affibody with amino-terminal HEHEHE sequence and carboxyl-terminal GGGC sequence by gene recombinant expression,which is the basis for invasive HER2 imaging with affibody. METHODS: The encoded affibody gene was optimized by codon preference of E. coli with gene designer software. The N-terminal of affibody was fused with HEHEHE sequence,while the C-terminal was fused with GGGC sequence. The synthetic gene was confirmed by Hind 3 endonuclease restriction and gene sequencing. The human epidermal growth factor receptor-2(HER2)affibody gene was sub-cloned into pET22b(+)plasmid and transformed into competent BL21(DE3)bacteria. The expression of modified affibody was induced with isopropyl Β-D-1-thiogalactopyranoside(IPTG)and identified by SDS-PAGE. The affibody was purified by nickel affinity binding and imidazole elution. The purified affibody was labeled with (68)Ga and its affinity was determined by saturation analysis with HER2-positive cells MDA-MB-361. RESULTS: The affibody gene containing N-terminal HEHEHE and C-terminal GGGC sequences were confirmed by Hind 3 endonuclease restriction and gene sequencing. A newly expressed 8×10(3) protein was expressed from the induced recombinant bacteria identified by SDS-PAGE after sub-cloning HER2 affibody gene into pET22b(+)plasmid,transforming recombinant plasmid into competent BL21(DE3)bacteria and inducing the recombinant bacteria with IPTG. The expressed protein was purified from nickel agarose by 60 mmol/L imidazole eluting. The affinity Kd value of (68)Ga labeled affibody to HER2 positive MDA-MB-361 cells was 1.5 nmol/L. CONCLUSION: The affiibody ZHER2V2 containing N-terminal HEHEHE and C-terminal GGGC was successfully prepared by gene optimization,recombinant expression and affinity purification.

18F-labeled pyrazolo[1,5-a]pyrimidine derivatives: synthesis from 2,4-dinitrobenzamide and tosylate precursors and comparative biological evaluation for tumor imaging with positron emission tomography.

We previously reported 18F-labeled pyrazolo[1,5-a]pyrimidine derivatives: 7-(2-[18F]fluoroethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile ([18F]1) and N-(2-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-ylamino)ethyl)-2-[18F]fluoro-4-nitro- benzamide ([18F]2). Preliminary biodistribution experiments of both compounds showed s slow clearance rate from excretory tissues which warranted further investigation for tumor imaging with PET. Here we modified [18F]1 and [18F]2 by introducing polar groups such as ester, hydroxyl and carboxyl and developed three additional 18F-18 labeled pyrazolo[1,5-a] pyrimidine derivatives: (3-Cyano-7-(2-[18F]fluoroethylamino)pyrazolo[1,5-a]-pyrimidin-5- yl)methyl acetate ([18F]3), 7-(2-[18F]fluoroethylamino)-5-(hydroxymethyl)pyrazolo[1,5-a]- pyrimidine-3-carbonitrile ([18F]4) and (S)-6-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-ylamino)-2-(2-[18F]fluoro-4-nitrobenzamido)hexanoic acid ([18F]5). The radiolabeled probes were synthesized by nucleophilic substitution of the corresponding tosylate and nitro precursors with 18F-fluoride. In Vitro studies showed higher uptake of [18F]3 and [18F]4 than that of [18F]5 by S180 tumor cells. In Vivo biodistribution studies in mice bearing S180 tumors showed that the uptake of both [18F]3 and [18F]4 in tumors displayed an increasing trend while the uptake of [18F]5 in tumor decreased through the course of the 120 min study. This significant difference in tumor uptake was also found between [18F]1 and [18F]2. Thus, we compared the biological behavior of the five tracers and reported the tumor uptake kinetic differences between 2-[18F]fluoroethylamino- and 2-[18F]fluoro-4-nitro- benzamidopyrazolo[1,5-a] pyrimidine derivatives.

Brown adipose tissue can be activated or inhibited within an hour before 18F-FDG injection: a preliminary study with microPET.

Brown adipose tissue (BAT) is emerging as a potential target for treating human obesity. It has been indicated that BAT is rich in innervations of sympathetic nerve control. Using (18)F-FDG microPET imaging, this study aims at evaluating how factors related to sympathetic activation/inhibition changed BAT metabolism of mice. BAT (18)F-FDG uptake were semiquantitatively evaluated in different groups of mice under temperature (cold or warm stimulus) or pharmacological interventions (norepinephrine, epinephrine, isoprenaline, or propranolol) and were compared with the corresponding controls. It was found that BAT activation can be stimulated by cold exposure (P = 1.96 × 10(-4)), norepinephrine (P = .002), or both (P = 2.19 × 10(-6)) within an hour before (18)F-FDG injection and can also be alleviated by warming up (P = .001) or propranolol lavage (P = .027). This preliminary study indicated that BAT function could be evaluated by (18)F-FDG PET imaging through short-term interventions, which paved the way for further investigation of the relationship between human obesity and BAT dysfunction.

Synthesis and biological evaluation of novel F-18 labeled pyrazolo[1,5-a]pyrimidine derivatives: potential PET imaging agents for tumor detection.

Two novel pyrazolo[1,5-a]pyrimidine derivatives, 7-(2-[(18)F]fluoroethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile ([(18)F]FEMPPC, [(18)F]1) and N-(2-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-ylamino)ethyl)-2-[(18)F]fluoro-4-nitrobenzamide ([(18)F]FCMPPN, [(18)F]2), have been designed and successively labeled with (18)F by the nucleophilic substitution employing tosylate and nitryl as leaving groups, respectively. The radiochemical synthesis of both compounds was completed within 60min with final high-performance liquid chromatography purification included. The corresponding radiochemical yields (without decay correction) were approximately 35% and 30%, respectively. Meanwhile, we compared the uptake characteristics of [(18)F]1 and [(18)F]2 with those of [(18)F]FDG and L-[(18)F]FET in S180 tumor cells. Furthermore, the tumor uptake of [(18)F]1 and [(18)F]2 was assessed in mice bearing S180 tumor and compared with [(18)F]FDG and L-[(18)F]FET in the same animal model. In vitro cell uptake studies showed [(18)F]1 had higher uptake than [(18)F]FDG, [(18)F]2 and L-[(18)F]FET over the 2h period. In ex vivo biodistribution showed tumor/brain uptake ratios of [(18)F]2 were 12.35, 10.44, 8.69 and 5.13 at 15 min, 30 min, 60 min and 120 min post-injection, much higher than those of L-[(18)F]FET (2.43, 2.54, 2.93 and 2.95) and [(18)F]FDG (0.59, 0.61, 1.02 and 1.33) at the same time point. What's more, the uptake of [(18)F]1 in tumor was 1.88, 4.37, 5.51, 2.95 and 2.88 at 5 min, 15 min, 30 min, 60 min and 120 min post-injection, respectively. There was a remarkable increasing trend before 30 min. The same trend was present for L-[(18)F]FET before 30 min and [(18)F]FDG before 60 min. Additionally, the tumor/brain uptake ratios of [(18)F]1 were superior to those of [(18)F]FDG at all the selected time points, the tumor/muscle and tumor/blood uptake ratios of [(18)F]1 at 30 min were higher than those of L-[(18)F]FET at the same time point. MicroPET image of [(18)F]1 administered into S180 tumor-bearing mouse acquired at 30 min post-injection illustrated that the uptake in S180 tumor was obvious. These results suggest that compound [(18)F]1 could be a new probe for PET tumor imaging.

Preoperative Localization of Adenomas in Primary Hyperparathyroidism: The Value of 11C-Choline PET/CT in Patients with Negative or Discordant Findings on Ultrasonography and 99mTc-Sestamibi SPECT/CT.

We aimed to assess the value of 11C-choline PET in patients with primary hyperparathyroidism and negative or discordant results on 99mTc-sestamibi imaging and neck ultrasound. Methods: Eighty-seven such patients were assessed and subsequently underwent parathyroidectomy. PET/CT image data were analyzed semiquantitatively using SUVmax and SUV ratios (target to contralateral thyroid gland and carotid artery). A positive PET/CT result was defined as focal uptake significantly higher than regular thyroid tissue. Ectopic foci were also considered positive. Inconclusive PET/CT cases were defined as a lesion with uptake equal to normal thyroid tissue. If no prominent or ectopic uptake was detectable, the PET/CT result was considered negative. Results: When dichotomizing the 11C-choline PET/CT imaging results by defining lesions with both positive and inconclusive uptake as positive, we found 84 of 92 lesions (91.3%) to have true-positive uptake whereas 8 lesions (8.7%) had false-positive uptake. One lesion showed false-negative uptake; the sensitivity was 98.8%. The corresponding positive predictive value for lesions was 91.3%. The mean SUVmax was 6.15 ± 4.92 in 72 lesions with positive uptake (70 patients) and 2.96 ± 2.32 in 20 lesions with inconclusive uptake (18 patients). Conclusion: These results in a large group of patients indicate that 11C-choline PET/CT is a promising tool for parathyroid adenoma localization when ultrasound and 99mTc-sestamibi imaging yield negative or discordant results.

Quantitative and Visual Characteristics of Primary Central Nervous System Lymphoma on 18F-FDG-PET.

Primary central nervous system lymphomas (PCNSLs) are rare progressive brain tumors, whose managements are significantly different from other solid tumors, especially glioblastomas. Therefore, an early diagnosis is of great significance. 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET), which can measure the glucose metabolic rate in the brain, is an increasingly common tool for early diagnosis. Twenty-five immunocompetent patients with PCNSL were reviewed in this study to describe the general characteristics of PCNSL patients' 18F-FDG-PET scans. Quantitative features included a radically enhanced maximum standardized uptake value (SUVmax) with a mean value of 23.8 ± 7.9 and a 5.8 ± 1.8 mean ratio of tumor-to-normal contralateral cortex activity (T/N). Visual characteristics, such as favored locations in the brain, lesion numbers, tumor shape, metabolic inhibition, and structural shift were determined as well. PCNSL was found to favor the cortex, especially the frontal lobe, followed by the basal ganglia and corpus callosum. All PCNSLs were near the lateral ventricular area. Tumor shapes were subdivided into three groups: diffuse, round, and irregular patterns. Reduced radiation was observed in the ipsilateral cortex, the basal ganglia and the contralateral cerebellum. The lateral ventricles were prone to be compressed on the side ipsilateral to the tumor, pushing the midline towards the contralateral side of the brain. In conclusion, aside from SUVmax and T/N values, other visual characteristics are also available to facilitate the differentiation of PCNSLs from other brain conditions on 18F-FDG-PET scans.

Improving evaluation of primary gastric malignancies by distending the stomach with milk immediately before 18F-FDG PET scanning.

UNLABELLED: This study was designed to investigate the feasibility and effectiveness of a modified protocol for (18)F-FDG PET that was proposed to improve the identification of primary gastric malignancies. METHODS: In the modified protocol, patients were asked to drink 300-500 mL of cow milk to distend the stomach immediately before PET scans instead of fasting all along. For investigation of the influence of ingested milk on (18)F-FDG distributions, 43 nondiabetic patients without documented gastric diseases underwent both empty- and distended-stomach PET scans (79 and 72 scans, respectively) in their serial follow-up studies. For the evaluation of proven gastric malignancies, 24 patients who underwent distended-stomach PET scans were compared with 17 patients who underwent conventional empty-stomach examinations. RESULTS: Ingestion of milk nearly 1 h after (18)F-FDG injection had no significant influence on distributions to the heart (P = 0.16), mediastinum (P = 0.50), and liver (P = 0.49), whereas the percentages of intense and moderate uptake in the stomach changed from 38.0% and 59.5% to 0% and 11.1%, respectively. With the normal gastric wall distended, malignant lesions were observed with higher contrast and clearer outlines, and some of them were detected at a small size (1.2 cm) at an early stage and with mild uptake. CONCLUSION: Gastric distention with milk just before (18)F-FDG PET is a simple and effective method for improving the evaluation of primary gastric malignancies.

Comparison among Reconstruction Algorithms for Quantitative Analysis of 11C-Acetate Cardiac PET Imaging.

Objective: Kinetic modeling of dynamic 11C-acetate PET imaging provides quantitative information for myocardium assessment. The quality and quantitation of PET images are known to be dependent on PET reconstruction methods. This study aims to investigate the impacts of reconstruction algorithms on the quantitative analysis of dynamic 11C-acetate cardiac PET imaging. Methods: Suspected alcoholic cardiomyopathy patients (N = 24) underwent 11C-acetate dynamic PET imaging after low dose CT scan. PET images were reconstructed using four algorithms: filtered backprojection (FBP), ordered subsets expectation maximization (OSEM), OSEM with time-of-flight (TOF), and OSEM with both time-of-flight and point-spread-function (TPSF). Standardized uptake values (SUVs) at different time points were compared among images reconstructed using the four algorithms. Time-activity curves (TACs) in myocardium and blood pools of ventricles were generated from the dynamic image series. Kinetic parameters K1 and k2 were derived using a 1-tissue-compartment model for kinetic modeling of cardiac flow from 11C-acetate PET images. Results: Significant image quality improvement was found in the images reconstructed using iterative OSEM-type algorithms (OSME, TOF, and TPSF) compared with FBP. However, no statistical differences in SUVs were observed among the four reconstruction methods at the selected time points. Kinetic parameters K1 and k2 also exhibited no statistical difference among the four reconstruction algorithms in terms of mean value and standard deviation. However, for the correlation analysis, OSEM reconstruction presented relatively higher residual in correlation with FBP reconstruction compared with TOF and TPSF reconstruction, and TOF and TPSF reconstruction were highly correlated with each other. Conclusion: All the tested reconstruction algorithms performed similarly for quantitative analysis of 11C-acetate cardiac PET imaging. TOF and TPSF yielded highly consistent kinetic parameter results with superior image quality compared with FBP. OSEM was relatively less reliable. Both TOF and TPSF were recommended for cardiac 11C-acetate kinetic analysis.

[Characteristics of physiological uptake of uterus and ovaries on 18F-fluorodeoxyglucose positron emission tomography].

OBJECTIVE: To observe the characteristics of the physiological uptake of uterus and ovaries on 18F-fluorodeoxyglucose positron emission tomography (FDG PET). METHODS: A total of 288 PET examinations performed in 247 women (164 with malignancies, 44 with benign diseases, and 39 without remarkable abnormality) were included for analysis, and clinical follow-ups were applied for at least 10 months to exclude pelvic diseases. The menstrual statuses, menstrual cycles, and related pelvic examinations with other modalities were inquired before each PET examination. PET scanning was performed from pelvis to neck with a Siemens ECAT EXACT HR + system. The uptake levels of uterus and ovaries were set as intense, moderate, and mild by comparing to liver uptake. RESULTS: In 116 patients (131 examinations ) with regular menstruation, the endometrial uptake, usually in inverted cone shape surrounded by relatively low-uptake uterine wall, was observed with two peaks in the early menstrual flow phase and in the mid-cycle respectively; the ovarian uptake was more prominent in the mid-cycle, with the foci of uptake in ovoidal shape and located at the left and/or right side superior-posterior to the bladder. From the early menstrual flow phase to the late secretory phase of the menstrual cycles, the probabilities of mild uptake in both endometrium and ovaries were 7%, 86%, 80%, 58%, 20%, 40%, 64%, and 59%, respectively, indicating that the late menstrual flow phase and the early proliferative phase had the least probability of intense or moderate uptake. No intense uptake was observed in the 17 patients (19 examinations) presenting remarkably irregular menstrual cycle, 112 patients (136 studies) in menopause for 3 months to 39 years, and 2 patients without menstruation yet. Only one patient within 1 year of menopause and a 14-year-old girl expected to start menstruation showed mild to moderate uptake in the endometrium. CONCLUSION: The physiological endometrial and ovarian uptakes have specific shapes and positions on 18F-FDG PET images, which correlates well with the menstrual phases.

Potential application of neogalactosylalbumin in positron emission tomography evaluation of liver function.

AIM: To investigate the evaluation of neogalactosylalbumin (NGA) for liver function assessment based on positron emission tomography technology. METHODS: Female Kunming mice were assigned randomly to two groups: fibrosis group and normal control group. A murine hepatic fibrosis model was generated by intraperitoneal injection of 10% carbon tetrachloride (CCl4) at 0.4 mL every 48 h for 42 d. 18F-labeled NGA ([18F]FNGA) was synthesized and administered at a dosage of 3.7 MBq/mouse to both fibrosis mice and normal control mice. Distribution of [18F]FNGA amongst organs was examined, and dynamic scanning was performed. Parameters were set up to compare the uptake of tracers by fibrotic liver and healthy liver. Serologic tests for liver function were also performed. RESULTS: The liver function of the fibrosis model mice was significantly impaired by the use of CCl4. In the fibrosis model mice, hepatic fibrosis was verified by naked eye assessment and pathological analysis. [18F]FNGA was found to predominantly accumulate in liver and kidneys in both control group (n = 21) and fibrosis group (n = 23). The liver uptake ability (LUA), peak time (Tp), and uptake rate (LUR) of [18F]FNGA between healthy liver (n = 8) and fibrosis liver (n = 10) were significantly different (P < 0.05, < 0.01, and < 0.05, respectively). LUA was significantly correlated with total serum protein level (TP) (P < 0.05). Tp was significantly correlated with both TP and glucose (Glu) concentration (P < 0.05 both), and LUR was significantly correlated with both total bile acid and Glu concentration (P < 0.01 and < 0.05, respectively). CONCLUSION: [18F]FNGA mainly accumulated in liver and remained for sufficient time. Functionally-impaired liver showed a significant different uptake pattern of [18F]FNGA compared to the controls.

Endometrial and ovarian F-18 FDG uptake in serial PET studies and the value of delayed imaging for differentiation.

PURPOSE: This study was designed to characterize the physiological endometrial and ovarian F-18 FDG uptake through analysis of clinical patients with serial PET follow ups (group 1) or who underwent delayed imaging (group 2). METHODS: Group 1 had 24 patients (14 premenopausal and 10 postmenopausal). Each patient underwent 2 to 4 serial FDG PET studies and summed to 57 studies. Group 2 included 15 premenopausal patients with delayed imaging 3 hours after injection. Ten of them showed endometrial uptake, and 8 showed intense uptake in 10 ovaries. Visual and semiquantitative methods were applied for analysis. RESULTS: By analysis of serial PET studies, endometrial and ovarian uptake showed some specific characteristics. Surrounded by a relatively low-uptake uterine wall, the inverted cone-shaped endometrium showed 2 peaks of uptake, one in early menstruation and the other in midcycle. The ovarian uptake was more prominent in the midcycle, and the foci of uptake had an ovoid shape and located at the left and/or right side superior-posterior to the bladder. For the postmenopausal and amenorrhea women (35 studies), only one study in a woman within 1 year of menopause showed mild endometrial and ovarian uptake. Compared with the imaging 1 hour after injection, the standardized uptake value increased in 2 of 10 endometria and 4 of 10 ovaries in the delayed imaging. CONCLUSION: Physiological endometrial and ovarian uptake can be identified on PET alone by their specific shape and position as well as their relation to the menstrual state, whereas delayed imaging was of little value for differentiation in this preliminary study.

Semiautomatic synthesis of 3'-deoxy-3'-[18F]fluorothymidine using three precursors.

To facilitate clinical studies with [18F]FLT, we modified 2-vessel [18F]FDG synthesis module (manufactured by CTI) to produce [18F]FLT. Three thymidine derivatives were used as precursors for [18F]FLT synthesis. Among these precursors, 3-N-t-butoxycarbonyl-[5'-O-(4,4'-dimethoxytrityl)-2'-deoxy-3'-O-(4-nitrobenzenesulfonyl)-beta-D-threopentofuranosyl]thymine (thymidine derivative II) gave the best radiochemical yield (37.9%) when the reaction was carried out at 140 degrees C for 5 min. This semiautomatic synthesis system was not only simple and convenient, but also showed good reproducibility. The total synthesis time was 50 minutes from the end of bombardment (EOB) by the use of this modified synthesizer (including the manual process).

11C-Acetate PET/CT Monitoring Therapy of Multiple Myeloma.

A 67-year-old man with newly diagnosed multiple myeloma underwent both FDG and C-acetate PET/CT sequentially on different days. There was increased FDG activity only in L1 vertebral body, but there was diffuse abnormal C-acetate activity throughout the skeletal system. After the successful therapy, the patient who was on remission clinically underwent follow-up PET/CT scans. Interestingly, L1 remained to have elevated FDG, although with less intensity. In contrast, there was no abnormal C-acetate activity anywhere in the body. The patient remained in remission clinically.

Solitary Plasmacytoma in the Renal Pelvis on 18F-FDG and 11C-Acetate PET/CT.

A 70-year-old man was incidentally found to have an occupying lesion in the left renal pelvis by ultrasonography during a routine health examination. CT images suggested renal cell carcinoma. FDG PET/CT scan was acquired for staging. The images did not reveal any hypermetabolic metastases. However, the metabolic activity of the lesion in the right renal pelvis was not unambiguously determined because of interference of radioactive urine. C-acetate PET/CT, on the other hand, clearly revealed increased activity in the left renal pelvis. Pathological examination demonstrated solitary extraosseous plasmacytoma.

Focal hepatic 11C-acetate activity on PET/CT scan due to lymphoid hyperplasia.

A 69-year-old woman complaining of abdominal bloating underwent ultrasonography, which revealed a small lesion in the left lobe of the liver. The lesion had elevated activity of both 18F-FDG and 11C-acetate on PET/CT scan and was suspected of being malignant. Postresection pathological examination demonstrated that this lesion was a focal intrahepatic lymphoid hyperplasia.

Kinetic analysis of dynamic (11)C-acetate PET/CT imaging as a potential method for differentiation of hepatocellular carcinoma and benign liver lesions.

OBJECTIVE: The kinetic analysis of (11)C-acetate PET provides more information than routine one time-point static imaging. This study aims to investigate the potential of dynamic (11)C-acetate hepatic PET imaging to improve the diagnosis of hepatocellular carcinoma (HCC) and benign liver lesions by using compartmental kinetic modeling and discriminant analysis. METHODS: Twenty-two patients were enrolled in this study, 6 cases were with well-differentiated HCCs, 7 with poorly-differentiated HCCs and 9 with benign pathologies. Following the CT scan, all patients underwent (11)C-acetate dynamic PET imaging. A three-compartment irreversible dual-input model was applied to the lesion time activity curves (TACs) to estimate the kinetic rate constants K1-k3, vascular fraction (VB) and the coefficient α representing the relative hepatic artery (HA) contribution to the hepatic blood supply on lesions and non-lesion liver tissue. The parameter Ki (=K1×k3/(k2 + k3)) was calculated to evaluate the local hepatic metabolic rate of acetate (LHMAct). The lesions were further classified by discriminant analysis with all the above parameters. RESULTS: K1 and lesion to non-lesion standardized uptake value (SUV) ratio (T/L) were found to be the parameters best characterizing the differences among well-differentiated HCC, poorly-differentiated HCC and benign lesions in stepwise discriminant analysis. With discriminant functions consisting of these two parameters, the accuracy of lesion prediction was 87.5% for well-differentiated HCC, 50% for poorly-differentiated HCC and 66.7% for benign lesions. The classification was much better than that with SUV and T/L, where the corresponding classification accuracy of the three kinds of lesions was 57.1%, 33.3% and 44.4%. CONCLUSION: (11)C-acetate kinetic parameter K1 could improve the identification of HCC from benign lesions in combination with T/L in discriminant analysis. The discriminant analysis using static and kinetic parameters appears to be a very helpful method for clinical liver masses diagnosis and staging.