Etofibrate enhances 123I-LDL-binding in human liver.

Etofibrate, a combination of fibric and nicotinic acid, is successfully used for the treatment of type IIb and IV hyperlipidemia. While an up-regulation of specific low density lipoproteins (LDL) binding sites in human platelets has been demonstrated, action on LDL-binding to the liver in patients and kinetic studies rare. This study aimed to investigate the influence of twice 500mg etofibrate daily given for 6 weeks on the in vivo binding of autologous LDL to the liver in 11 patients, 6 males, 5 females; aged 37-57 years, suffering from mixed hyperlipidemia. Etofibrate enhanced in vivo liver uptake of (123)I-LDL by 16.1% at mean, shortened plasma decay of LDL and improved lipid profile: serum total cholesterol was lowered by 14.9%, LDL-cholesterol was lowered by 22.2% and high-density lipoprotein (HDL)- cholesterol was increased by 10.9%. These findings are documenting a beneficial effect of the drug at the LDL liver receptor level in vivo.

Triggering radiation alarm at security checks. Patients should be informed even after diagnostic nuclear medicine procedures.

During the last few years an increasing number of nuclear medicine patients in various countries evoked a radiation alarm after therapeutic or diagnostic procedures, and even after passive exposure. A prospective calculation of activity retention in the patient's body is difficult due to extremely high variation of uptake and kinetics. Furthermore, different sensitivities and distances of the detectors make a prospective calculation even more difficult. In this article a number of cases are being reported, related problems are discussed and the surprisingly very limited literature reviewed. In order to minimize problems after eventually triggering alarms, we strongly recommend that each patient receives a certificate providing personal data, tracer, dose, half-life of the radionuclide, type and date of procedure applied as well as the nuclear medicine unit to contact for further information. Furthermore, a closer cooperation and exchange of information between the authorities and local nuclear medicine societies, would be welcome.

Iodine-125-fibrinogen kinetics in the rabbit arterial wall.

Elevated fibrinogen has been claimed as an independent risk factor for the development of atherosclerosis. Incorporation of fibrinogen into human atherosclerotic lesions has been demonstrated. We assessed in a rabbit model of experimental atherosclerosis, biodistribution as well as kinetics and vascular uptake of (125)I-fibrinogen. Rabbits aged 6 months were fed a 1% cholesterol supplemented diet. After experimental de-endothelialization of rabbit aorta using a Fogarthy catheter, (125)I-fibrinogen uptake was enhanced by more than one order of magnitude as compared to intact segments covered by endothelium. Six rabbits per group were examined. Even re-endothelialized segments showed a significantly higher uptake of the radiolabeled protein. Maximum arterial uptake varied between 12 (de- and re-endothelialized segments) and 24h (intact areas) after injection of (125)I-fibrinogen. In conclusion, these experiments for the first time suggest the increased uptake of radiolabeled fibrinogen in the aortic de-endothelized wall in rabbits.

Radioiodine therapy induces dose-dependent in vivo oxidation injury: evidence by increased isoprostane 8-epi-PGF(2 alpha).

UNLABELLED: 131I is the treatment of choice for differentiated thyroid cancer and hyperthyroidism. A relationship between low-density lipoprotein oxidation and radioiodine therapy-related side effects, consequently inducing increased formation of 8-epi-prostaglandin F(2 alpha) (PGF(2 alpha)) in situ, has recently been reported by several investigators. Isoprostanes, among them 8-epi-PGF(2 alpha), have been associated with increased oxidation injury due to various pathologic conditions in vivo. The aim of this study was to investigate the possible induction of oxidative stress as a consequence of (131)I therapy. METHODS: 8-epi-PGF(2 alpha) was examined in plasma, serum, and urine in 42 patients undergoing radioiodine treatment of hyperthyroidism or thyroid cancer. The 8-epi-PGF(2 alpha) levels were analyzed daily for 1 wk and thereafter at different points up to 12 wk after treatment. RESULTS: The isoprostane levels showed an increase after application of radioiodine in all investigated compartments. The effect was significantly higher and longer lasting after higher-activity therapy (2,960 or 7,400 MBq) than after lower-activity therapy (185 or 740 MBq). CONCLUSION: These findings document a significant, dose-dependent in vivo oxidation injury as a consequence of therapeutic radioiodine application to the salivary gland.

Usefulness of brain natriuretic peptide levels to discriminate patients with stable angina pectoris without and with electrocardiographic myocardial ischemia and patients with healed myocardial infarction.

Brain natriuretic peptide (BNP) levels were measured in 100 patients with coronary heart disease (CHD) who underwent myocardial stress thallium-201 single-photon emission computed tomography (30 with stable angina without basal electrocardiographic ischemia and no perfusion defects, 31 with angina with electrocardiographic ischemia and reversible perfusion defects, and 39 with myocardial infarction and irreversible defects) and in 42 controls. BNP levels progressively increased in patients with CHD and were significantly greater in patients with ischemia (p <0.01) and infarction (p <0.001) compared with controls and subjects with angina. BNP concentration was correlated positively (r = 0.923, p <0.001) with perfusion defect extent and inversely (r = -0.690, p <0.001) with the left ventricle ejection fraction (not different in the subjects examined).

Association between brain natriuretic peptide and extracellular water in hemodialysis patients.

BACKGROUND: Brain natriuretic peptide (BNP) is a hormone released by the left ventricle (LV) as a consequence of pressure or volume load. BNP increases in left ventricle hypertrophy (LVH), LV dysfunction, and it can also predict cardiovascular mortality in the general population as well as those undergoing hemodialysis (HD). We investigated the association between BNP and volume load in HD patients. METHODS: We studied 32 HD patients (60 +/- 17.1 years) treated thrice-weekly for at least 6 months. Exclusion criteria were: LV dysfunction, atrial fibrillation, malnutrition. Blood chemistries and BNP were determined on mid-week HD day. Blood pressure (BP) and cardiac diameters were determined on mid-week inter-HD day by using 24-hour ambulatory blood pressure monitoring and echocardiography. Bioimpedance was performed after HD and extracellular water (ECW%), calculated as a percentage of total body water, was considered as the index of volume load. RESULTS: Patients were divided into quartiles of 8 patients depending on the BNP value: 1st qtl BNP < or =45.5 pg/ml (28.4 +/- 10.9 pg/ml), 2nd qtl BNP > 45.5 pg/ml and < or =99.1 pg/ml (60.9 +/- 15.8 pg/ml), 3rd qtl BNP > 99.1 pg/ml and < or =231.8 pg/ml (160.5 +/- 51.8 pg/ml), 4th qtl BNP > 231.8 pg/ml (664.8 +/- 576.6 pg/ml). No inter-quartile differences were reported in age, HD age, body mass index spKt/V, or blood chemistries. As expected patients in the 4th BNP quartile showed the highest values of 24-hour pulse pressure (PP) and LV mass index (LVMi). The study of body composition revealed significant differences in ECW%, which was higher in the 4th quartile when compared to the others (4th q: 50 +/- 9.6%, vs 1st q. 40.1 +/- 2.4%, 2nd q. 41.9 +/- 5%, 3rd q. 42.8 +/- 6.9%). Using multiple stepwise linear regression where BNP was the dependent variable, and PP and ECW% the independent variables, only ECW% maintained statistical significance as a predictor of BNP levels (PP: Beta = 0.86, p = 0.58; ECW%: Beta = 0.64, p < 0.001 p < 0.001). CONCLUSIONS: Few studies have investigated the relationship between plasma BNP and volume load, and direct evidence is lacking. We used bioimpedance and the determination of ECW% to assess volume state in HD patients finding an association between BNP and ECW. The increased synthesis and release of BNP from the LV in HD patients appear to be mainly related to volume stress rather than to pressure load.

Correlation of lipoprotein(a) levels and myocardial stress thallium scintigraphy pattern in different entities of CHD severity.

BACKGROUND: Higher levels of lipoprotein(a) confer an increased risk for coronary heart disease (CHD). Apo-E genotype (APO-E) also plays a role, the APO-E epsilon 4 allele being associated with CHD. Furthermore, higher Lp(a) concentrations are correlated with APO-E epsilon 4 allele presence. The study was performed to investigate the relationship of Lp(a) and APO-E with the functional status of coronary arteries as evaluated by myocardial scintigraphy. PATIENTS AND METHODS: We studied 70 patients (27 F and 43 M; mean age: 55 +/- 6 yrs.) consecutively referred for CHD, and 50 normal sex and age-matched controls. Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apo-AI, apo-B, Lp(a) levels (ELISA), Lp(a) isoforms (Immuno Blotting) and APO-E (PCR) were measured in all subjects. Only CHD patients underwent a myocardial tomographic stress thallium scintigraphy (201Tl-SPECT); the SPECT pattern was classified as follows: no perfusion defects (unstable angina group = 1), reversible defects at stress images (ischemia group = 2), fixed defects (infarction group = 3). RESULTS: Lp(a) medians were significantly higher than controls in group 1 (p < 0.05), 2 (p < 0.001) and 3 (p = 0.00). Low molecular weight isoforms (B, S1, S2) were significantly more frequent in all CHD-patients vs. controls (p < 0.05), whereas APO-E genotypes did not differ among controls and patients. Multiple regression analysis showed family history (p < 0.001) to be the only independent predictive variable of CHD severity correlated to the scintigraphic pattern. CONCLUSION: Among the considered biological parameters in our patients only Lp(a) plasma levels are related to the entity of ischemic cardiac wall damage as evaluated by 201Tl-SPECT.

Radioidine therapy temporarily increases circulating endothelial cells and decreases endothelial progenitor cells.

BACKGROUND: Radiotherapy can cause vascular injury. No data on radioiodine therapy and vascular damage are available. MATERIAL AND METHODS: We examined the number of circulating endothelial cells (CEC) and circulating endothelial progenitor cells (CEPC) before therapy 1, 2, 3 and 5 days as well as 1, 2, 3, 4, 6, 8, 10, and 12 weeks after therapy with (131)I at doses ranging from 5-200 mCi. The individual number of CEC and CEPC is associated with the presence of risk factors. RESULTS: Irrespective of prevalues, CEC exhibited a significant dose-dependent temporary increase reaching the maximum in weeks 1 and 2. In contrast, CEPC show a decrease at the same time. CONCLUSIONS: These results indicate that (131)I-therapy induces a dose-dependent radiation injury at the vascular wall level enhancing endothelial desquamation and reducing reendothelialization and thereby a proatherogenic stage. The clinical consequence of these findings still needs to be assessed.

Prickly pear induces upregulation of liver LDL binding in familial heterozygous hypercholesterolemia.

BACKGROUND: The hypoglycemic effect of prickly pear is well known by native local Indian population since a long time. Beside the beneficial effects on lipid metabolism, oxidation injury and platelet function has been claimed in experimental animals. We recently found an upregulation of apo-B/E receptor. MATERIAL AND METHODS: We therefore examined 10 patients with isolated heterozygous familial hypercholesterolemia (FH) being enrolled in a dietary run-in phase of 6 weeks after dietary counselling and a further 6 weeks of prickly pear addition. Uptake of autologous (123)I-radiolabeled LDL was determined at entry as well as after 6 weeks of daily prickly pear ingestion. RESULTS: We found a significant (p < 0.0001) increase in LDL-uptake by the liver (24.5 +/- 4.9 vs. 31.1 +/- 5.2%) and an enhanced decay in circulating blood. Total (298.0 --> 268.0 mg/dl; p < 0.0001) and LDL-cholesterol (210.5 --> 176.4 mg/dl; p = 0.0001) were significantly affected, while HDL (p = 0.0629) and triglycerides were not. CONCLUSIONS: These findings demonstrate a significant upregulation of (123)I-LDL binding by prickly pear in FH-patients invivo and indicate that prickly pear exerts a significant hypolipidemic action via receptor upregulation.

67Ga-SPECT/CT with a hybrid system in the clinical management of lymphoma.

PURPOSE: The purpose of this study was to investigate the added value of co-registered fusion imaging using a hybrid system in patients with lymphoma. METHODS: Twenty-four lymphoma patients underwent (67)Ga-SPECT/CT using a hybrid tomograph consisting of a dual-head, variable-angle gamma camera and a low-dose X-ray tube. Results were compared with those of SPECT alone. RESULTS: Forty-five lesions were identified by SPECT alone, while 49 were detected by SPECT/CT. Forty out of the 45 lesions observed on SPECT were confirmed as lymphoma, but five were due to other causes (thoracic aorta blood pool activity, sialoadenitis in the submandibular gland, bowel activity, rib fracture and bone marrow activation due to radiotherapy). SPECT/CT identified nine more neoplastic lesions compared with SPECT alone: four areas of radiopharmaceutical accumulation were observed in para-aortic lymph nodes, three in the spleen, one in the liver and one in para-iliac lymph nodes. In five cases, SPECT/CT provided additional anatomical information over SPECT alone. In four patients, four large areas of (67)Ga uptake (one mediastinal, two supraclavicular and one para-aortic) were better characterised; in one subject uptake was localised in the seventh thoracic vertebra only by SPECT/CT. Hybrid imaging provided additional data in 13 patients (54.2%), thus inducing oncologists to reconsider the therapeutic approach in eight subjects (33.2%): unnecessary treatment was avoided in four (16.6%) while therapy was altered in another four (16.6%). CONCLUSION: SPECT/CT hybrid system is able to provide information not obtained by SPECT alone. It allows the anatomical localisation of lymphoma and physiological radiopharmaceutical uptake, facilitates the diagnosis of tumours located in the abdomen (subdiaphragmatic lesions) and provides information that may cause a change in therapeutic strategy.

Problems and pitfalls in vulvar and cervical cancer sentinel node scintigraphy

After the introduction for penile cancer, the sentinel lymph node imaging is increasingly applied in various types of cancer. After the initial learning phase, 105 patients with vulvar and 24 with cervical cancer have been investigated. In vulvar cancer all the imaged sentinel nodes were discovered by the portable probe intraoperatively. No false negative sentinel node was observed. The most critical issue is the tracer application. Performed strictly intradermally, the sentinel node shows up immediately. Concomitant use of isosulfan blue dye did not improve the results and was stopped therefore. Similarly, more superficial (intra/subendothelial) application brings up better results as compared to deeper injection in cervical cancer patients. No false negative results were seen. Apparently, an almost 100%detection is possible. Our findings clearly show that tracer application is the key for successful imaging. If not done properly, sentinel node may appear later or may even more likely be missed.

Após a introdução para câncer do pênis, a imagem do linfonodo sentinela é cada vez mais aplicada nos diversos tipos de câncer. Após a fase inicial de aprendizagem, 105 pacientes com câncer vulvar e 24 com câncer cervical foram investigados. No câncer vulvar todas as imagens de nodos sentinela foram descobertas por sonda portátil durante o exame. Nenhum nodo sentinela falso negativo foi observado. A questão mais crítica é a aplicação do traçador. Realizada pela via intradérmica, o nodo sentinela surge imediatamente. O corante isosulfan blue não melhora os resultados e seu uso concomitante foi abandonado. Do mesmo modo, a aplicação mais superficial (intra/subendotelial) apresenta melhores resultados quando comparada com a administração mais profunda em pacientes com câncer cervical. Não foram observados resultados falsos negativos. Aparentemente, uma detecção de aproximadamente 100% é possível. Nossos achados mostram claramente que a administração do traçador é um ponto chave para uma imagem com qualidade. Se não for feita corretamente, o nodo sentinela pode aparecer tardiamente ou pode até ser perdido.