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.

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.

[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.

[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.

[Synthesis and preliminary studies of O-(2-[18F] fluoroethyl)-L-tyrosine as a positron emission tomography imaging agent].

OBJECTIVE: To develop a 18F-labeled amino acid, O-(2-[18F]fluoroethyl) - L-tyrosine(18F-FET), as a positron emission tomography (PET) tracer for imaging cerebral tumors. METHODS: 18F-FET was synthesized. Preclinical studies including sterility, endotoxin, and toxicity tests were performed. Two brain tumor cases were studied using 18F-FET and compared with 18F-FDG. RESULTS: Radiochemical purity of 18F-FET was over 95% which remained stable for 6 hours. The 18F-FET injection was sterile and its endotoxin content accorded with the standards of Chinese Pharmacopoeia. The uptake of 18F-FET in the normal brain tissues was significantly lower than that of the tumor, and the images of the brain tumor were clearer than those of 18F-FDG. CONCLUSION: 18F-FET can accumulate in the tumor tissues to give high quality images. It suggests that 18F-FET may be a safe and effective tracer for brain tumor imaging.