ω-Halofatty acids: A probe for mitochondrial membrane integrity

Long-chain -halofatty acids, especially -¹²³I-iodoheptadecanoic acid (IHA), are widely used clinically as radiopharmaceuticals for functional heart imaging. The metabolic interpretation of the various elimination rates, however, remains in dispute. It has been previously shown (Kloster and Stöcklin 1982) that in isolated perfused guinea-pig hearts halide diffusion from the mitochondrion to the blood is the rate-determining step of IHA pharmacokinetics in normal myocardium. We have now extended these in vitro experiments to normal and globally ischaemic isolated perfused rabbit hearts. Again, in normal hearts a single phase iodide elimination half-time (14.3±2.1 min) was observed. In hearts made globally ischaemic for 90 min, the iodide elimination was biphasic with a first fast phase (T_1/2=3.8±0.49 min) and a late slow phase (T _1/2=60.5±14.0 min). The first fast phase is attributed to iodide ion released by residual -oxidation (more rapid than in normal hearts due to damaged membranes in ischaemia), while the late slow phase is explained by -oxidation of IHA slowly released by hydrolysis of intracellular lipid stores. These data were compared with published data from investigations in patients which seem to support our interpretation.     

Synthesis of 2-[123I and 124I]-iodoisonicotinic acid hydrazide—potential radiotracers for tuberculosis

The radiochemical syntheses of methyl 2-[¹²³I]-iodoisonicotinate, 2-[¹²³I]-iodoisonicotinic acid hydrazide and 2-[¹²⁴I]-iodoisonicotinic acid hydrazide was accomplished. Iodine-123 was incorporated in the methyl ester molecule by an exchange reaction in glacial acetic acid. The average efficiency of iodine exchange reaction was (92.6 ± 4.5)%. This radiotracer was extracted with ether and the solvent was evaporated. The residue was re-dissolved in anhydrous ethanol and treated with hydrazine under anhydrous conditions to obtain 2-[¹²³I]-iodoisonicotinic acid hydrazide. The overall radiochemical yield was 69%. Biodistribution data of both radio-tracers in male Sprague-Dawley rats were collected. This is the first report of SPECT radiopharmaceuticals which may be useful for differential diagnosis of intracranial masses (tuberculoma vs glioma), and CNS tuberculosis in immunosuppressed subjects.     

Estimation of the area at risk in myocardial infarction of rats by means of I-123 β-methyliodophenyl pentadecanoic acid imaging

Clinical investigations have suggested that the defects in SPECT images of a free fatty acid analog, I-123 beta-methyliodophenyl pentadecanoic acid (BMIPP) may indicate the ischemic risk area. To elucidate whether I-123 BMIPP can indicate the area at risk of ischemia, ex-vivo autoradiography was performed in rats whose left coronary artery was occluded for 60 min and then reperfused. I-123 BMIPP was injected at the acute stage (n = 10), or the subacute stage (7 days after reperfusion; n = 9). Infarction and the area at risk were identified by triphenyl tetrazolium chloride staining and injection of methylene blue during religation just before sacrifice, respectively. The BMIPP uptake in the risk area was significantly lower than that in the remote area at the acute (risk, 53.7+/-23.3% of the uptake at right ventricle, mean +/- SD; remote, 109.3+/-11.8%; p < 0.01) and subacute (risk, 52.5+/-11.5%; remote, 97.9+/-14.3%; p < 0.01) stages. In addition, the area with reduced uptake of I-123 BMIPP showed a significant correlation with the area at risk both at the acute (r = 0.98, p < 0.01) and subacute (r = 0.92, p < 0.01) stages. In conclusion, the area at risk can be evaluated by I-123 BMIPP both at the acute and subacute stages.     

青海高原13种野生植物油脂中ω-6脂肪酸和ω-3脂肪酸分析

1996年青海省测试计算中心结合省科技厅专家基金课题,对青海境内26科70种油脂植物中14种脂肪酸成分进行分析、鉴定,结果发现有13种植物中ω-6脂肪酸和ω-3脂肪酸之比小于4∶1,人类的进化过程表明这样的     

Study of leaving groups for the preparation of [ω-18F]fluorofatty acids via nucleophilic fluorination and its application to the synthesis of 17-[18F]fluoro-3-methylheptadecanoic acid

The effect of leaving groups on the introduction of [¹⁸F]fluorine into fatty acids via nucleophilic fluorination has been systematically studied. It has been proved that tosylate and bromide are the most reactive among such leaving groups as chloride, bromide, iodide, mesylate, tosylate and triflate. This result has been applied to the synthesis of 17-[¹⁸F]fluoro-3-methylheptadecanoic acid used in routine medical studies. Using methyl 17-bromo-3-methylheptadecanoate, the ¹⁸F-labeled 3-methyl-branched fatty acid has been prepared in a radiochemical yield of 36–58% (based on ¹⁸F⁻) with radiochemical purities of > 97%.     

Fatty acid myocardial imaging using 123I-β-methyl-iodophenyl pentadecanoic acid (BMIPP): comparison of myocardial perfusion and fatty acid utilization in canine myocardial infarction (Occlusion and reperfusion model)

To evaluate the relationship between myocardial perfusion and fatty acid metabolism in canine myocardial infarction, 16 dogs were studied using thallium and ¹²³I--methyl-iodophenyl pentadecanoic acid (BMIPP). Eight dogs (group A) had left anterior coronary arterial occlusion (6 h ligation), 6 dogs (group B) had reperfusion (3 h ligation and 1 h reperfusion) and 2 dogs served as the normal control. Myocardial imaging with BMIPP was excellent, owing to its higher uptake and longer retention in myocardium and rapid blood disappearance in addition to diminished liver and lung uptake. The mean half time value which was generated from the BMIPP myocardial washout curve, was significantly larger in the reperfused myocardium. The gamma camera imaging showed uncoupling of BMIPP and thallium (BMIPP uptake greater than thallium uptake) in five dogs in group B. On the other hand, all dogs in group A had a persistent defect in BMIPP and thallium uptake. Our findings indicate that the combination of BMIPP and thallium for myocardial imaging supply different information about the zone of infarction and ischemia, which may be useful for the assessment of myocardial viability.     

What is the relationship between exercise and metabolic abnormalities? A review of the metabolic syndrome

Prevention of the metabolic syndrome and treatment of its main characteristics are now considered of utmost importance in order to combat the epidemic of type 2 diabetes mellitus and to reduce the increased risk of cardiovascular disease and all-cause mortality. Insulin resistance/hyperinsulinaemia are consistently linked with a clustering of multiple clinical and subclinical metabolic risk factors. It is now widely recognised that obesity (especially abdominal fat accumulation), hyperglycaemia, dyslipidaemia and hypertension are common metabolic traits that, concurrently, constitute the distinctive insulin resistance or metabolic syndrome. Cross-sectional and prospective data provide an emerging picture of associations of both physical activity habits and cardiorespiratory fitness with the metabolic syndrome. The metabolic syndrome, is a disorder that requires aggressive multi-factorial intervention. Recent treatment guidelines have emphasised the clinical utility of diagnosis and an important treatment role for 'therapeutic lifestyle change', incorporating moderate physical activity. Several previous narrative reviews have considered exercise training as an effective treatment for insulin resistance and other components of the syndrome. However, the evidence cited has been less consistent for exercise training effects on several metabolic syndrome variables, unless combined with appropriate dietary modifications to achieve weight loss. Recently published randomised controlled trial data concerning the effects of exercise training on separate metabolic syndrome traits are evaluated within this review. Novel systematic review and meta-analysis evidence is presented indicating that supervised, long-term, moderate to moderately vigorous intensity exercise training, in the absence of therapeutic weight loss, improves the dyslipidaemic profile by raising high density lipoprotein-cholesterol and lowering triglycerides in overweight and obese adults with characteristics of the metabolic syndrome. Lifestyle interventions, including exercise and dietary-induced weight loss may improve insulin resistance and glucose tolerance in obesity states and are highly effective in preventing or delaying the onset of type 2 diabetes in individuals with impaired glucose regulation. Randomised controlled trial evidence also indicates that exercise training decreases blood pressure in overweight/obese individuals with high normal blood pressure and hypertension. These evidence-based findings continue to support recommendations that supervised or partially supervised exercise training is an important initial adjunctive step in the treatment of individuals with the metabolic syndrome. Exercise training should be considered an essential part of 'therapeutic lifestyle change' and may concurrently improve insulin resistance and the entire cluster of metabolic risk factors.     

Uptake of iodine-123-α-methyl tyrosine by gliomas and non-neoplastic brain lesions

Using single-photon emission tomography (SPET), the radiopharmaceuticall,-3-iodine-123--methyl tyrosine (IMT) has been applied to the imaging of amino acid transport into brain tumours. It was the aim of this study to investigate whether IMT SPET is capable of differentiating between high-grade gliomas, low-grade gliomas and non-neoplastic brain lesions. To this end, IMT uptake was determined in 53 patients using the triple-headed SPET camera MULTISPECT 3. Twenty-eight of these subjects suffered from high-grade gliomas (WHO grade III or IV), 12 from low-grade gliomas (WHO grade II), and 13 from non-neoplastic brain lesions, including lesions after effective therapy of a glioma (five cases), infarctions (four cases), inflammatory lesions (three cases) and traumatic haematoma (one case). IMT uptake was significantly higher in high-grade gliomas than in low-grade gliomas and non-neoplastic lesions. IMT uptake by low-grade gliomas was not significantly different from that by non-neoplastic lesions. Diagnostic sensitivity and specificity were 71% and 83% for differentiating high-grade from low-grade gliomas, 82% and 100% for distinguishing high-grade gliomas from non-neoplastic lesions, and 50% and 100% for discriminating low-grade gliomas from non-neoplastic lesions. Analogously to positron emission tomography with radioactively labelled amino acids and fluorine-18 deoxyglucose, IMT SPET may aid in differentiating high-grade gliomas from histologically benign brain tumours and non-neoplastic brain lesions; it is of only limited value in differentiating between non-neoplastic lesions and histologically benign brain tumours.     

Potential prognostic implications of myocardial thallium-201 and iodine-123-beta-methylpentadecanoic acid dual scintigraphy in patients with Anderson–Fabry disease

Annals of Nuclear Medicine - Information on the relationship between myocardial damage assessed by myocardial scintigraphy and prognosis in patients with Anderson–Fabry disease (AFD) is...     

Evaluation of [1-11C]-α-aminoisobutyric acid for tumor detection and amino acid transport measurement: spontaneous canine tumor studies

Alpha-aminoisobutyric acid (AIB), or -methyl alanine, is a nonmetabolized amino acid transported into cells, particularly malignant cells, predominantly by the A amino acid transport system. Since it is not metabolized, [1-¹¹C]-AIB can be used to quantify A-type amino acid transport into cells using a relatively simple compartmental model and quantitative imaging procedures (e.g. positron tomography). The tissue distribution of [1-¹¹C]-AIB was determined in six dogs bearing spontaneous tumors, including lymphosarcoma, osteogenic sarcoma, mammary carcinoma, and adenocarcinoma. Quantitative imaging with tissue radioassay confirmation at necropsy showed poor to excellent tumor localization. However, in all cases the concentrations achieved appear adequate for amino acid transport measurement at known tumor locations. The observed low normal brain (due to blood-brain barrier exclusion) and high (relative to brain) tumor concentrations of [1-¹¹C]-AIB suggest that this agent may prove effective for the early detection of human brain tumors.     

No-carrier-added radiosynthesis of [123I]HIPDM: N,N,N′-trimethyl-N′-(2-hydroxy-3-methyl-5-[123I]iodobenzyl)-1,3-propanediamine

The multi-millicurie production of the SPECT radiopharmaceutical N,N,N′-trimethyl-N′-(2-hydroxy-3-methyl-5-[¹²³I]iodobenzyl)-1,3-propanediamine ([¹²³I]HIPDM) in high specific activity is described. Using no-carrier-added electrophilic iododeprotonation reactions and HPLC purification, [¹²³I]HIPDM can be isolated in 70–76% radiochemical yield and specific activity >2000 Ci/mmol within an overall preparation time of 75 min. This methodology is readily adapted to the clinical setting, and eliminates the need for co-injection of macroscopic HIPDM in SPECT imaging procedures.     

Diagnostic usefulness of an amino acid tracer, α-[N-methyl-11C]-methylaminoisobutyric acid (11C-MeAIB), in the PET diagnosis of chest malignancies

Objectives

Although positron emission tomography (PET) using [¹⁸F]-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) is established as one of the first-choice imaging modalities in the diagnosis of chest malignancies, there are several problems to solve in clinical practice, such as false positive uptake in inflammatory diseases. The aim of this study was to evaluate the clinical usefulness of an amino acid tracer, α-[N-methyl-¹¹C]-methylaminoisobutyric acid (¹¹C-MeAIB), in the diagnosis of chest malignancies, in combination with ¹⁸F-FDG.

Setting

Fifty-nine cases (57 patients, 66 ± 12 years old) who consulted to our institution for the wish to receive differential diagnosis of chest diseases were included. Purpose of the studies were as follows: differential diagnosis of newly developed lung nodules, n = 22; newly developed mediastinal lesions, n = 20; and both, n = 17 (including lung cancer: n = 19, lymphoma: n = 1, other cancers: n = 2, sarcoidosis: n = 15, non-specific inflammation: n = 18, other inflammatory: n = 4, respectively). Whole-body static PET or PET/CT scan was performed 20 and 50 min after the IV injection of ¹¹C-MeAIB and ¹⁸F-FDG, respectively.

Results

¹¹C-MeAIB uptake of malignant and benign lesions was statistically different both in pulmonary nodules (p < 0.005) and in mediastinal lesions (p < 0.0005). In visual differential diagnosis, ¹¹C-MeAIB showed higher results (specificity: 73 %, accuracy: 81 %), compared to those in ¹⁸F-FDG (60, 73 %, respectively). In cases of sarcoidosis, ¹¹C-MeAIB showed higher specificity (80 %) with lower uptake (1.8 ± 0.7) in contrast to the lower specificity (60 %) with higher uptake of ¹⁸F-FDG (7.3 ± 4.5).

Conclusions

¹¹C-MeAIB PET/CT was useful in the differential diagnosis of pulmonary and mediastinal mass lesions found on CT. ¹¹C-MeAIB PET or PET/CT showed higher specificity than that of ¹⁸F-FDG PET/CT in differentiating between benign and malignant disease. Our data suggest that the combination of ¹⁸F-FDG and ¹¹C-MeAIB may improve the evaluation of chest lesions, when CT and ¹⁸F-FDG PET/CT are equivocal.     

The reduction of the influence of formation properties on the calibration of a prompt γ-ray interaction analysis probe

A procedure for reducing the influence of the formation on the calibration of a prompt neutron activation analysis probe is given. It is shown, using Monte-Carlo simulation techniques, that the ratio of the normalised γ-ray flux to the neutron flux is a smooth function of the neutron migration length in the formation. By measuring this parameter it is possible to predict the normalised γ-ray flux and remove the formation effects from the measured γ-ray flux.     

The dosimetry of iodine-123 labelled 2β-carbomethoxy-3β-(4-iodophenyl)tropane

This report documents the radiation dosimetry of iodine-123 labelled 2-carbomethoxy-3-(4-iodophenyl)tropane [¹²³I]-CIT in humans. The mean absorbed doses for various organs and the effective dose equivalent were estimated from whole-body scans, blood samples and single-photon emission tomography scans acquired up to 22 h after the injection of a known amount of tracer. The basal ganglia, the liver and the lower large intestinal wall received the highest mean absorbed doses of 0.270 mGy/MBq, 0.038 mGy/MBq and 0.034 mGy/MBq, respectively. The effective dose equivalent for adults was estimated using 11 organs and the ICRP-87 radiation dose model and was 0.031 mSv/MBq. The radiation dose to the basal ganglia limits the maximum injected activity of [¹²³I]-CIT to 185 MBq for a single study.     

ω-iodophenyl fatty acids: A convenient method of radioiodination

A solid-phase radioiodination technique for ω-iodophenyl fatty acids using ammonium sulfate is described. The radioiodinations are (1) regioselective, (2) high in yield (95%), (3) short in reaction time (1 h) and (4) capable of yielding high specific activity products although at lower yields. Purification is exceptionally simple: a single passage through an ion exchange column to remove unreacted ¹I⁻ is all that is required. Syntheses of several ω-iodophenyl fatty acids are also described.     

Percutaneous radiofrequency ablation of liver tumors with the LeVeen probe: is roll-off predictive of response?

PURPOSE: The LeVeen radiofrequency (RF) probe uses roll-off of electrical impedance as the endpoint for RF cautery of hepatic tumors. The purpose of this study is to determine the relation of roll-off to local control of hepatic tumors. MATERIALS AND METHODS: Twenty hepatic tumors, including 10 hepatomas and 10 metastases, were treated. Lesions ranged from 1.4 cm to 6.0 cm in diameter; 13 (57%) were smaller than 3.0 cm. Each lesion was ablated with use of the LeVeen 15-gauge RF needle according to the manufacturer's protocol. Five patients underwent chemoembolization the day before. Patients were followed up with contrast-enhanced computed tomography or magnetic resonance imaging at 1 month and every 3 months thereafter. RESULTS: Among the 20 lesions, roll-off was achieved at all burn locations in 11 (55%), no burn locations in eight (40%), and two of three burn locations in one (5%). Roll-off was observed in all patients who had undergone chemoembolization the day before. Six local recurrences occurred, five after RF ablation without roll-off and one after RF ablation with roll-off. According to life-table analysis, the local recurrence rate at 6 months without roll-off was 43% and with roll-off was 15% (P =.024; OR = 8.3; 95% CI = 0.93-66). CONCLUSION: Roll-off is a significant predictor of local control after RF ablation. Strategies to enhance roll-off, such as concurrent embolization, may be important to optimize the therapeutic effect of this device.     

High uptake of L-3-[123I]iodo-α-methyl tyrosine in pilocytic astrocytomas

Despite a favourable prognosis, pilocytic astrocytomas may exhibit signs of malignancy on various neuroimaging modalities. This retrospective analysis was conducted to determine whether scintigraphic features of malignancy are also found on single-photon emission tomography (SPET) using L-3-[¹²³I]iodo-!-methyl tyrosine (IMT) as a tracer. Twenty patients with pilocytic astrocytomas were retrospectively selected from a large series of patients referred for the evaluation of primary or recurrent brain tumours. IMT SPET was performed in 16 patients, positron emission tomography (PET) using 2-[¹⁸F]fluoro-2-deoxy-D-glucose (FDG) was available in 10 of the patients and SPET using technetium-99m tetrofosmin or thallium-201 had been performed in 11. Image analysis was performed using standard protocols to determine how many patients exceeded the respective thresholds of malignancy. Features of malignancy were found in 7/16 IMT SPET studies, in 7/10 FDG PET studies and in 7/11 of the residual SPET investigations. A significant correlation of tumour size and IMT uptake in primary pilocytic astrocytomas indicated partial volume effects to partly account for the differential uptake behaviour (n=10, r=0.87, P<0.05). Differences in IMT uptake in primaries (1.7ǂ.6, n=10) and in recurrent tumours (2.3ǂ.7, n=6) did not attain statistical significance. IMT SPET results indicative of malignancy are regularly found in pilocytic astrocytomas, despite their good prognosis. No uptake may be detected in largely cystic or in small tumours.