Synthesis of fluorine-18-labeled ciprofloxacin for PET studies in humans

Ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-quinoline-3-carboxylic acid), a widely-prescribed antibiotic, was labeled with fluorine-18 with the aim to perform positron emission tomography studies in humans for pharmacokinetic measurements. Due to a lack of chemical activation of ciprofloxacin for a direct nucleophilic exchange reaction a novel two-step synthetic approach, which employed an activated 6-fluoro-7-chloro substituted precursor molecule, was developed. The radiosynthesis yielded, starting from 52.5 +/- 11.3 GBq of [(18)F]fluoride, 1.3 +/- 0.6 GBq (n = 13) [(18)F]ciprofloxacin ready for intravenous administration in about 130 min synthesis time. A series of analytical tests was performed in order to prove the identity of the radiolabeled compound and its suitability for human applications.     

Nonuniformity in myocardial accumulation of fluorine-18-fluorodeoxyglucose in normal fasted humans

In initial studies using fluorine-18-fluorodeoxyglucose (FDG) in normal fasted subjects, we observed disparities in the regional myocardial accumulation of this tracer. Accordingly, we systematically evaluated regional myocardial FDG accumulation in comparison with regional myocardial perfusion assessed with oxygen-15-water and oxidative metabolism assessed with carbon-11-acetate in nine normal subjects (four studied after a 5-hr fast and five studied both fasted and following glucose loading). Under fasting conditions, myocardial accumulation of FDG in the septum and anterior wall averaged 80% of that in the lateral and posterior walls (p less than 0.03). In contrast, after glucose loading the regional distribution of myocardial FDG accumulation became more homogeneous. Regional myocardial perfusion, oxidative metabolism, and accumulation of carbon-11-acetate were homogeneous under both conditions. Thus, under fasting conditions there are regional variations in myocardial accumulation of FDG, which are visually apparent, are not associated with concomitant changes in oxidative metabolism or perfusion, and cannot be attributed to partial-volume effects. This significant heterogeneity may limit the specificity of PET with FDG for detecting myocardial ischemia in fasting subjects.     

PET imaging of musculoskeletal tumours with fluorine-18 alpha-methyltyrosine: comparison with fluorine-18 fluorodeoxyglucose PET

Fluorine-18 labelled alpha-methyltyrosine (FMT) was developed for positron emission tomography (PET) imaging, and its potential for clinical application in patients with brain tumours has been demonstrated. This is the first trial to compare FMT with 18F-fluoro-2-deoxy-D-glucose (FDG) for the evaluation of musculoskeletal tumours. Seventy-five patients were examined with both FMT- and FDG-PET within a 2-week period. Imaging findings were visually inspected in conjunction with computed tomography and/or magnetic resonance imaging, and standardized uptake values (SUVs) for both FMT and FDG in lesions were also generated and compared with histological findings. A significant correlation between FMT and FDG SUVs was found for all lesions (r=0.769, P<0.0001), and mean values for malignant tumours were significantly higher than those for benign lesions in both FMT- and FDG-PET. The diagnostic sensitivities and specificities for malignancy were 72.7% and 84.9%, respectively, using FMT with a cut-off SUV of 1.2, and 72.7% and 66.0%, respectively, using FDG with a cut-off SUV of 1.9. The resultant accuracy with FMT was 81.3%, higher than that for FDG (68.0%), and the difference with respect to specificity was significant (chi2cal=5.0625, P<0.05). On the other hand, while a significant correlation was found between malignant tumour grade and SUV with both FMT- (rho=0.656) and FDG-PET (rho=0.815), only the latter demonstrated significant differences among grades I, II and III. FMT and FDG for PET appear equally effective at detecting musculoskeletal tumours. In evaluating musculoskeletal tumours, FMT may be superior to FDG in the differentiation between benign and malignant tumours, while FDG may be the better choice for non-invasive malignancy grading.     

Assessment of response to cancer therapy using fluorine-18-fluorodeoxyglucose and positron emission tomography

In order to evaluate the usefulness of 18F-FDG PET in the assessment of therapeutic effects, FDG-PET studies were performed both before and after therapy in 26 patients with miscellaneous malignant tumors. The change in FDG uptake by therapy was compared with the change in tumor size and prognosis. All 26 lesions had a high FDG uptake before therapy. Five of seven lesions which had a relatively low FDG uptake before therapy showed no change or increase in tumor size by therapy. The decreased FDG uptake after therapy was more prominent in the partial response group than in the no change group. FDG uptake before therapy in the non-relapse group was higher than that in the relapse group. However, a decreased FDG uptake did not necessarily indicate a good prognosis. One patient with no change in tumor size and a decreased FDG uptake had no recurrence. This suggests that FDG-PET has a complementary role in the assessment of therapeutic effects.     

Evaluation of liver tumors using fluorine-18-fluorodeoxyglucose PET: characterization of tumor and assessment of effect of treatment.

To evaluate glucose metabolism in patients with tumors involving the liver, 35 patients with liver lesions had PET using 18F-2-fluoro-2-deoxy-D-glucose (FDG). FDG (148 MBq) was injected and radioactivity of the tumor was scanned dynamically by PET. The rate constants (k1, k2, k3, k4) of FDG in a metabolic model were calculated. The results were compared to hexokinase activity in the excised tumor specimens. k3 was found to reflect tumor hexokinase activity. When k3 was used as an index (cut-off value: 0.025), it was possible to distinguish benign and malignant tumors. k4 was significantly higher in hepatocellular carcinoma. By using k3 and k4 as indices, one could assess the degree of differentiation of hepatocellular carcinoma. After treatment, k3 decreased according to the effectiveness of therapy and thus may be a useful index for quantitatively assessing tumor viability.     

Radiation exposure to sonographers from fluorine-18-FDG PET patients

OBJECTIVE: We estimated the amount of radiation exposure to sonographers from patients who were injected with 18F-fluorodeoxyglucose (FDG) at 2 and 3 h postinjection. METHODS: We studied 8 patients who were given between 380-420 MBq 18F-FDG. The patients were measured with a RADOS RDS-120 dosimeter between 2 and 3 h after FDG injection. The dosimetry measurement was taken at a distance of 0.5 m from the injected patient, a distance used by a sonographer to perform an abdominal ultrasound. Measurements were taken at the levels of the sonographer's shoulder, abdomen, and gonads. RESULTS: At the first measurement at 2 h, the mean exposures to the shoulder, abdomen, and gonads of the sonographer in pSv/h were 31.9+/-11.3, 37.1+/-9.5, and 32.8+/-11.8, respectively. At 3 h, the mean exposures to the shoulder, abdomen, and gonads were 21.5+/-4.2, 20.2+/-5.8, and 19.6+/-4.9, respectively. CONCLUSION: The amount of radiation exposure to a sonographer is minimal. Radiation exposure risks should be considered, however, if the sonographer comes into daily, repeated contact with patients who have been given 18F-FDG.     

Normal variants in [18F]-fluorodeoxyglucose PET imaging

The number of fluorodeoxyglucose PET applications is increasing. In the process of reading fluorodeoxyglucose-PET scans, nuclear medicine physicians encounter a wide variety of normal findings, which must be recognized to determine the best management for patients. It is important to recognize and understand normal variants to avoid misinterpretation of more serious pathology. This article reviews different patterns of physiologic fluorodeoxyglucose uptake including changes with age.     

南宁地区住民X线诊断检查频率

本文用检查外周血染色体畸变的方法,对下半身(HBI)和全淋巴区照射(TLI)患者的全身血液平均受照剂量,进行了实验研究.本研究共观察了19名接受⁶⁰Co γ线治疗的患者,萁中HBI10名,TLI 9名,病人的受照剂量均为8 Gy.放疗前采每位患者的静脉血样,将染色体畸变检查结果作为对照值.放疗后24小时再做一次检查,计算照射诱发的双着丝粒(dic)产额,代入经过剂量率影响校正的回归方程,反堆出HBI和TLI患者的全身血液平均受照剂量,分别为155cGy和40cGy.本研究推算出的剂量与患者照射后的临床表现是符合的.     

放疗患者全身血液平均受照剂量的估算

本文用检查外周血染色体畸变的方法,对下半身(HBI)和全淋巴区照射(TLI)患者的全身血液平均受照剂量,进行了实验研究.本研究共观察了19名接受⁶⁰Co γ线治疗的患者,萁中HBI10名,TLI 9名,病人的受照剂量均为8 Gy.放疗前采每位患者的静脉血样,将染色体畸变检查结果作为对照值.放疗后24小时再做一次检查,计算照射诱发的双着丝粒(dic)产额,代入经过剂量率影响校正的回归方程,反堆出HBI和TLI患者的全身血液平均受照剂量,分别为155cGy和40cGy.本研究推算出的剂量与患者照射后的临床表现是符合的.     

497例眼晶状体调查

本文用检查外周血染色体畸变的方法,对下半身(HBI)和全淋巴区照射(TLI)患者的全身血液平均受照剂量,进行了实验研究.本研究共观察了19名接受⁶⁰Co γ线治疗的患者,萁中HBI10名,TLI 9名,病人的受照剂量均为8 Gy.放疗前采每位患者的静脉血样,将染色体畸变检查结果作为对照值.放疗后24小时再做一次检查,计算照射诱发的双着丝粒(dic)产额,代入经过剂量率影响校正的回归方程,反堆出HBI和TLI患者的全身血液平均受照剂量,分别为155cGy和40cGy.本研究推算出的剂量与患者照射后的临床表现是符合的.     

Clinical usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose in the diagnosis of liver tumors

We studied various liver tumors by positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) to examine the diagnostic usefulness of this technique. We also examined the relation between findings on FDG-PET and the characteristics of hepatocellular carcinoma. FDG-PET was performed in 78 patients with liver tumors, including 53 with primary liver cancer [48 hepatocellular carcinomas (HCC) and 5 cholangiocellular carcinomas (CCC)], 20 with metastatic liver cancer, 2 with liver hemangioma, and 3 with focal nodular hyperplasia. For quantitative evaluation, a region of interest (ROI) was placed over the entire tumor region, at the level of the maximum diameter of the tumor. A background ROI was then placed over the non-tumor region of the liver. The average activity within each ROI was subsequently corrected for radioactive decay, and the standardized uptake value (SUV) was calculated by dividing the tissue activity by the injected dose of radioactivity per unit body weight. SUV ratio was expressed as the tumor-to-non-tumor ratio of the SUV. The median SUV was significantly lower in HCC than in metastatic live cancer or CCC, and the median SUV ratio was significantly lower in HCC than in metastatic liver cancer or CCC. The median SUV was not higher in multiple HCC than in single HCC, but the median SUV ratio was significantly higher in multiple HCC than in single HCC. The median SUV and the median SUV ratio were significantly higher in the presence of portal vein thrombosis than in the absence of such thrombosis. The Cancer of the Liver Italian Program score and the alpha-fetoprotein value correlated significantly with both the SUV and SUV ratio. These results suggest that FDG-PET is clinically useful not only for the differential diagnosis of liver tumors but also for evaluation of the clinical characteristics of HCC.     

Radiation-induced inhibition of tumor growth as monitored by PET using L-[1-11C]tyrosine and fluorine-18-fluorodeoxyglucose.

The potential use of PET to monitor radiotherapeutic effects on tumors has been evaluated with L-[1-11C]tyrosine and 18FDG. Single x-ray doses of 10, 30, or 50 Gy have been applied to rhabdomyosarcoma tumors growing in the flank of rats. Dose-dependent reductions of tracer uptake were registered by PET 4 and 12 days after treatment. These later effects on tracer uptake appeared to correlate with changes in tumor volume. Therefore, PET using L-[1-11C]tyrosine and 18FDG is suitable to monitor kinetics of tumor growth and tumor regression after radiotherapy. Direct effect on tracer uptake was not observed within 8 hr after irradiation. This indicates that, using PET, early predictions on the outcome of radiotherapy are not possible. When combining a radiation treatment with hyperthermia, radiation-induced inhibition of tumor growth was clearly enhanced. Tracer uptake remained at the pretreatment value, possibly due to invasion of host cells. From these experiments, it can be concluded that it is difficult to monitor a combined treatment of radiation and hyperthermia by PET.     

Studies of primary central nervous system lymphoma with fluorine-18-fluorodeoxyglucose positron emission tomography.

Primary CNS lymphoma is a rare and highly malignant primary brain tumor. Ten patients with biopsy-proven primary CNS lymphoma were studied with 18F-2-fluoro-2-deoxy-D-glucose (FDG) and positron emission tomography (PET) to demonstrate the findings in patients with this tumor. The accumulation of FDG in primary CNS lymphoma is similar to that seen in anaplastic gliomas and is significantly more prominent than in low grade astrocytomas (p = 0.001). Steroid therapy substantially reduced the amount of FDG uptake in the one case studied both before and after its administration. The difference in FDG uptake between steroid-treated and untreated cases of primary CNS lymphoma, however, did not reach statistical significance (p = 0.40). Primary CNS lymphoma, like gliomas, suppresses the metabolism of both contiguous and distant but functionally linked areas of the brain. This study thus shows that the metabolic behavior of primary CNS lymphoma, as monitored by FDG-PET, resembles that of malignant glial tumors.     

Comparison of fluorine-18-2-fluorodeoxyglucose and gallium-67 citrate imaging for detection of lymphoma

Patients with lymphomas are conventionally imaged with [67Ga]citrate for tumor detection and determination of dissemination. Fluorine-18-2-fluoro-2-deoxy-D-glucose [( 18F]FDG) is a radiopharmaceutical that accumulates into tissues where glucose utilization is enhanced, such as tumors. Six cancer patients (five non-Hodgkin's lymphomas, one endodermal retroperitoneal sinus carcinoma) were imaged with [18F]FDG and [67Ga]citrate whole-body scintigraphies in order to compare the sensitivities of these two tumor imaging radiopharmaceuticals. Among the five untreated lymphoma patients, two 67Ga scans and four [18F]FDG scans were positive; in the patient with the retroperitoneal carcinoma who had a positive [18F]FDG scan before treatment, both scans were negative after treatment. Fluorine-18 FDG may be a more sensitive tumor-detecting radiopharmaceutical for non-Hodgkin's lymphoma than [67Ga]citrate.     

A method for comparing different procedures of estimating regional glucose metabolism using fluorine-18-fluorodeoxyglucose.

The purpose of this paper is to describe a method for determining whether a particular procedure for estimating regional metabolism using the deoxyglucose tracer analogue yields better data than another in terms of subsequent statistical analysis. The method is based on a simple model of regional cerebral glucose metabolism with three potential sources of metabolic variability, namely individual differences in cerebral metabolic rate, consistent regional differences and error. When the literature rate constants were compared to a dynamic procedure for estimating regional rate constants in patients with Huntington's Disease, the literature values were clearly superior in that the error component was approximately half (18.5 versus 39.3%). Although these results cannot be generalized to all procedures for estimating regional glucose metabolism, the method can be applied to determine if a particular procedure will be more sensitive than another to differences between groups.