PET imaging of the dopamine transporter with 18F-FECNT: a polar radiometabolite confounds brain radioligand measurements.

18F-2beta-Carbomethoxy-3beta-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane (18F-FECNT), a PET radioligand for the dopamine transporter (DAT), generates a radiometabolite that enters the rat brain. The aims of this study were to characterize this radiometabolite and to determine whether a similar phenomenon occurs in human and nonhuman primate brains by examining the stability of the apparent distribution volume in DAT-rich (striatum) and DAT-poor (cerebellum) regions of the brain. METHODS: Two rats were infused with 18F-FECNT and sacrificed at 60 min. Extracts of brain and plasma were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometric (LC-MS) techniques. Two human participants and 3 rhesus monkeys were injected with 18F-FECNT and scanned kinetically, with serial arterial blood analysis. RESULTS: At 60 min after the injection of rats, 18F-FECNT accumulated to levels about 7 times higher in the striatum than in the cortex and cerebellum. The radiometabolite was distributed at equal concentrations in all brain regions. The LC-MS techniques identified N-dealkylated FECNT as a major metabolite in the rat brain, and reverse-phase HPLC detected an equivalent amount of radiometabolite eluting with the void volume. The radiometabolite likely was 18F-fluoroacetaldehyde, the product expected from the N-dealkylation of 18F-FECNT, or its oxidation product, 18F-fluoroacetic acid. The distribution volume in the cerebellum increased up to 1.7-fold in humans between 60 and 300 min after injection and 2.0 +/- 0.1-fold (mean +/- SD; n = 3) in nonhuman primates between 60 and 240 min after injection. CONCLUSION: An 18F-fluoroalkyl metabolite of 18F-FECNT originating in the periphery confounded the measurements of DAT in the rat brain with a reference tissue model. Its uniform distribution across brain regions suggests that it has negligible affinity for DAT (i.e., it is an inactive radiometabolite). Consistent with the rodent data, the apparent distribution volume in the cerebellum of both humans and nonhuman primates showed a continual increase at late times after injection, a result that may be attributed to entry of the radiometabolite into the brain. Thus, reference tissue modeling of 18F-FECNT will be prone to more errors than analysis with a measured arterial input function.     

Measurement of kinetic parameters in skeletal muscle by magnetic resonance imaging with an intravascular agent.

The purpose of this work was to investigate the use of an intravascular contrast agent to determine perfusion kinetics in skeletal muscle. A two-compartment kinetic model was used to represent the flux of contrast agent between the intravascular space and extravascular extracellular space (EES). The relationship between the image signal-to-noise ratio (SNR) and errors in estimating permeability surface area product (Ktrans), interstitial volume (ve), and plasma volume (vp) for linear and nonlinear curve-fitting methods was estimated from Monte Carlo simulations. Similar results were obtained for both methods. For an image SNR of 60, the estimated errors in these parameters were 10%, 22%, and 17%, respectively. In vivo experiments were conducted in rabbits to examine physiological differences between these parameters in the soleus (SOL) and tibialis anterior (TA) muscles in the hind limb. Values for Ktrans were significantly higher in the SOL (3.2+/-0.9 vs. 2.0+/-0.5x10(-3) min-1), as were values for vp (3.4+/-0.8 vs. 2.1+/-0.7%). Differences in ve for the two muscles (8.7+/-2.2 vs. 8.5+/-1.6%) were not found to be significant. These results demonstrate that relevant physiological metrics can be calculated in skeletal muscle using MRI with an intravascular contrast agent.     

Advanced thyroid carcinoma: an experience of 385 cases.

AIMS: To report clinical outcomes of a large series of cases with advanced thyroid cancer. STUDY DESIGN: Three hundred and eighty-five patients at the UICC stages III and IV were selected for the study with thyroid cancer. RESULTS: Papillary carcinoma and sclerosing carcinoma have better survival than the Hürthle cell and insular types. Lymphatic metastasis does not appear to worsen the prognosis. All the tumour forms offer the chance of long survival. CONCLUSIONS: Surgical treatment is the primary treatment of thyroid carcinoma. The combined treatments of surgery, metabolic beam therapy, suppressive hormone therapy, radiotherapy and chemotherapy cure a high percentage of patients with the tumour at an advanced stage.     

Safety considerations for operating room personnel during hyperthermic intraoperative intraperitoneal chemotherapy perfusion.

The new treatment strategy for Peritoneal Surface Malignancy combines a cytoreductive surgery and perioperative intraperitoneal chemotherapy. Cytoreduction removes all macroscopic tumor. Intraperitoneal chemotherapy avoids implantation of microscopic residual tumor cells on intra-abdominal surfaces when it is administered intraoperatively and/or early in the postoperative period. Delivering cytotoxic drugs directly into the peritoneal cavity maximizes dose intensity and minimizes systemic toxicity. Hyperthermia is selectively cytotoxic for malignant cells and potentiates the effect of chemotherapy. Implementation of this procedure makes the perioperative personnel to face a risk of exposure to cytotoxic agents. Furthermore, peritonectomies and electro-evaporation of tumor nodules are performed with high voltage electrocautery, generating a large amount of surgical smoke during several hours. Inhalation of these fumes may be also a risk for healthcare workers. In this article, we analyse in depth these new risks of the operating room personnel, we review the literature, and we give guidelines for secure performance of cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy, as well as for early postoperative intraperitoneal chemotherapy administration. These new procedures are safe techniques for patients and healthcare workers provided adequate policies are adopted to avoid occupational exposure.     

Sex differences in the clinical presentation and management of airflow obstruction.

The aim of the present study was to explore differences in the clinical expression, clinical diagnoses and management of airway diseases in a primary-care setting. Patients aged >or=35 yrs who had ever smoked were enrolled when they presented for any reason to one of eight rural primary-care practices. Respiratory symptom questionnaires and spirometry were administered. In total, 1,034 patients had acceptable and reproducible spirometry, of whom 550 (53%) were males and 484 (47%) were females. Males smoked more than females (41.2 versus 29.2 pack-yrs) respectively, and were more likely to have a pre-bronchodilator forced expiratory volume in one second/forced vital capacity <0.70 at 22.4 versus 11.8%, respectively. However, more females than males reported breathlessness (51.0 versus 42.8%, respectively), a prior diagnosis compatible with airflow obstruction and taking respiratory medications (23.4 versus 14.9%, respectively). In conclusion, the current results suggest that females are more likely than males to report breathlessness and be prescribed respiratory medications independent of differences in the severity of airflow obstruction.     

Hypoxic ventilatory response in successful extreme altitude climbers.

A very high ventilatory response to hypoxia is believed necessary to reach extreme altitude without oxygen. Alternatively, the excessive ventilation could be counterproductive by exhausting the ventilatory reserve early on. To test these alternatives, 11 elite climbers (2004 Everest-K2 Italian Expedition) were evaluated as follows: 1) at sea level, and 2) at 5,200 m, after 15 days of acclimatisation at altitude. Resting oxygen saturation, minute ventilation, breathing rate, hypoxic ventilatory response, maximal voluntary ventilation, ventilatory reserve (at oxygen saturation = 70%) and two indices of ventilatory efficiency were measured. Everest and K2 summits were reached 29 and 61 days, respectively, after the last measurement. Five climbers summited without oxygen, the other six did not, or succeeded with oxygen (two climbers). At sea level, all data were similar. At 5,200 m, the five summiters without oxygen showed lower resting minute ventilation, breathing rate and ventilatory response to hypoxia, and higher ventilatory reserve and ventilatory efficiency, compared to the other climbers. Thus, the more successful climbers had smaller responses to hypoxia during acclimatisation to 5,200 m, but, as a result, had greater available reserve for the summit. A less sensitive hypoxic response and a greater ventilatory efficiency might increase ventilatory reserve and allow sustainable ventilation in the extreme hypoxia at the summit.     

Combined transbronchial needle aspiration and positron emission tomography for mediastinal staging of NSCLC.

There are no data available combining transbronchial needle aspiration (TBNA) of mediastinal lymph nodes and positron emission tomography (PET) in the staging of nonsmall cell lung cancer (NSCLC). The aim of the current study was to determine if these two methods can enhance the negative predictive value of the individual modality alone, for a specific lymph node station, and if this integrated approach can reduce the number of mediastinoscopies. A total of 113 patients with enlarged mediastinal lymph nodes (> or = 1 cm), who underwent both TBNA and PET scanning, were included. In 51 patients, histopathology, confirmed by surgical lymph node dissection, was compared with PET results and TBNA. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy to detect malignant lymphadenopathy was 68 (13/19), 89 (119/134), 46 (13/28), 95 (119/125) and 86% (132/152) for PET, respectively; 54% (6/11), 100 (53/53), 100 (6/6), 91 (53/58) and 92% (59/64), respectively for TBNA; and 100 (11/11), 94 (50/53), 79 (11/14), 100 (50/50) and 95 (61/64) for combined TBNA and PET, respectively. Combination of transbronchial needle aspiration and positron emission tomography has the potential to allow adequate mediastinal staging of nonsmall cell lung cancer with enlarged lymph nodes in most patients without the need for mediastinoscopy.