Background-Pollution by particulates has been consistently associated with increased cardiovascular morbidity and mortality. However, the mechanisms responsible for these effects are not well-elucidated. Methods and Results-To assess to what extent and how rapidly inhaled pollutant particles pass into the systemic circulation, we measured, in 5 healthy volunteers, the distribution of radioactivity after the inhalation of "Technegas," an aerosol consisting mainly of ultrafine 99m Technetium-labeled carbon particles (Ͻ100 nm). Radioactivity was detected in blood already at 1 minute, reached a maximum between 10 and 20 minutes, and remained at this level up to 60 minutes. Thin layer chromatography of blood showed that in addition to a species corresponding to oxidized 99m Tc, ie, pertechnetate, there was also a species corresponding to particle-bound 99m Tc. Gamma camera images showed substantial radioactivity over the liver and other areas of the body. Conclusions-We conclude that inhaled 99m Tc-labeled ultrafine carbon particles pass rapidly into the systemic circulation, and this process could account for the well-established, but poorly understood, extrapulmonary effects of air pollution.

The mechanisms of particulate pollution-related cardiovascular morbidity and mortality are not well understood. We studied the passage of radioactively labeled ultrafine particles after their intratracheal instillation. Hamsters received a single intratracheal instillation of 100 microg albumin nanocolloid particles (nominal diameter < or = 80 nm) labeled with 100 microCi technetium-99m and were killed after 5, 15, 30, and 60 min. In blood, radioactivity, expressed as percentage of total body radioactivity per gram blood, amounted to 2.88 +/- 0.80%, 1.30 +/- 0.17%, 1.52 +/- 0.46%, and 0.21 +/- 0.06% at 5, 15, 30, and 60 min, respectively. Thin-layer chromatography showed only one peak of radioactivity corresponding to unaltered (99m)Tc-albumin nanocolloid. In the liver, radioactivity, expressed as percentage of total radioactivity per organ, amounted to 0.10 +/- 0.07%, 0.23 +/- 0.06%, 1.24 +/- 0.27%, and 0.06 +/- 0.02% at 5, 15, 30, and 60 min, respectively. Lower values were observed in the heart, spleen, kidneys, and brain. Dose dependence was assessed at 30 min following instillation of 10 microg and 1 microg (99m)Tc-albumin per animal (n = 3 at each dose), and values of the same relative magnitudes as after instillation of 100 microg were obtained. We conclude that a significant fraction of (99m)Tc-albumin, taken as a model of ultrafine particles, rapidly diffuses from the lungs into the systemic circulation.

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Summary:Background: Invasive electroencephalogram (EEG) studies are often considered necessary to localize the epileptogenic zone in partial epilepsies associated with focal dysplastic lesions (FDL). Our aim was to evaluate the relationships between subtraction ictal SPECT coregistered with magnetic resonance imaging (MRI) (SISCOM) hyperperfusion clusters and MRI-visible FDL, and to establish a preliminary algorithm for a noninvasive presurgical evaluation protocol for MRI-visible FDLs in patients with refractory epilepsy.Methods: Fifteen consecutive patients with refractory partial epilepsy and a single MRI-visible FDL underwent a noninvasive presurgical evaluation including SISCOM. Each hyperperfusion cluster was visually analyzed, automatically quantitated, and its distance form the lesion as outlined on the MRI was measured. In patients who underwent surgery, the volumes of resected brain tissue containing the FDL, the SISCOM hyperperfusion cluster, and surrounding regions were assessed on postoperative MRI and correlated with surgical outcome.Results: Fourteen of the 15 patients (93%) showed SISCOM hyperperfusion overlapping with the FDL. The FDL was detected only after reevaluation of the MRI guided by the ictal SPECT in 7 of the 15 patients (47%). Four distinct hyperperfusion patterns were observed, representing different degrees of seizure propagation. Nine patients have been operated on. Five have been seizure-free since surgery and one since a reoperation. The degree of resection of the MRI-visible FDL was the major determinant of surgical outcome. Full resection of the SISCOM hyperperfusion cluster was not required to render a patient seizure-free.Conclusion: Detailed analysis of SISCOM hyperperfusion patterns is a promising tool to detect subtle FDL on MRI and to establish the epileptic nature of these lesions noninvasively. Overlap between the SISCOM hyperperfusion cluster and MRI-visible FDL in a noninvasive presurgical evaluation with concordant data may suffice to proceed to epilepsy surgery aimed at removing the MRI-visible FDL and the part of the hyperperfusion cluster within and immediately surrounding the FDL. Key Words: Refractory epilepsy-Focal dysplastic lesions-Focal cortical dysplasia-Ictal SPECT-SISCOMEpileptogenic zone-Epilepsy surgery-Surgical outcome.A key point in the surgical planning of patients with focal dysplastic lesions (FDL) and refractory seizures is the localization of the portion of the epileptogenic zone extending beyond the visible lesion that needs to be resected (1-6). These surrounding regions may harbor microscopic pathology or be immediately engaged in the seizure following rapid propagation, thus needing to be resected (4,7-9). Some data suggest that subtraction ictal SPECT coregistered with magnetic resonance imaging (MRI) (SISCOM) (10) can indicate the region of seizure onset. The potential of SISCOM hyperperfusion, however, to represent a true surrogate of the ictal onset zone-eventually substituting for the information provided by intracranial electrodeshas ye...

We performed post hoc analyses on the utility of pretherapeutic and early interim 68 Ga-DOTATOC PET tumor uptake and volumetric parameters and a recently proposed biomarker, the inflammationbased index (IBI), for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumor (NET) patients treated with 90 Y-DOTATOC in the setting of a prospective phase II trial. Methods: Forty-three NET patients received up to 4 cycles of 90 Y-DOTATOC at 1.85 GBq/ m 2 /cycle with a maximal kidney biologic effective dose of 37 Gy. All patients underwent 68 Ga-DOTATOC PET/CT at baseline and 7 wk after the first PRRT cycle. 68 Ga-DOTATOC-avid tumor lesions were semiautomatically delineated using a customized SUV thresholdbased approach. PRRT response was assessed on CT using RECIST 1.1. Results: Median progression-free survival and overall survival (OS) were 13.9 and 22.3 mo, respectively. An SUV mean higher than 13.7 (75th percentile) was associated with better survival (hazard ratio [HR], 0.45; P 5 0.024), whereas a 68 Ga-DOTATOCavid tumor volume higher than 578 cm 3 (75th percentile) was associated with worse OS (HR, 2.18; P 5 0.037). Elevated baseline IBI was associated with worse OS (HR, 3.90; P 5 0.001). Multivariate analysis corroborated independent associations between OS and SUV mean (P 5 0.016) and IBI (P 5 0.015). No significant correlations with progression-free survival were found. A composite score based on SUV mean and IBI allowed us to further stratify patients into 3 categories with significantly different survival. On early interim PET, a decrease in SUV mean of more than 17% (75th percentile) was associated with worse survival (HR, 2.29; P 5 0.024). Conclusion: Normal baseline IBI and high 68 Ga-DOTATOC tumor uptake predict better outcome in NET patients treated with 90 Y-DOTATOC. This method can be used for treatment personalization. Interim 68 Ga-DOTATOC PET does not provide information for treatment personalization.

Although the use of HEPES, acetate and succinate as buffering substances yielded comparable results, only acetate is currently recognized as a substance for pharmaceutical use and also for human use. Therefore, acetate buffer should be used for (68)Ga-Dotatoc synthesis. The semi-automated system allowed for a shorter radiosynthesis time, thereby increasing the overall yield.

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A comparative study was carried out on two promising presynaptic dopamine transporter single-photon emission tomography (SPECT) radioligands with a fast pharmacokinetic profile, 123I-FP-beta-CIT (FP) and 99mTc-TRODAT-1 (TR), in order to assess their differential diagnostic power in early parkinsonism and their sensitivity for detection of disease progression. This cross-sectional study was conducted on 96 patients with early-stage parkinsonism referred in a tertiary clinical setting. Mean disease duration was 2.0+/-1.3 years, and patients had a modified Hoehn and Yahr (H&Y) stage of 1-2 (average 1.2). Forty-seven patients received TR, and 49 received FP. In both groups, ten patients with normal presynaptic function were included as a control population; all other patients were clinically diagnosed as having idiopathic Parkinson's disease. Groups were matched for gender, age, disease duration and modified H&Y stage. Triple-head gamma camera SPECT was analysed using a semiquantitative index of transporter binding (BI). Discriminant analysis with cross-validation resulted in a maximal classification accuracy for FP of 93% (sensitivity 95% and specificity 86%) for the contralateral putamen BI. For TR, the corresponding values were 87% accuracy, 92% sensitivity and 70% specificity. For FP, disease duration was correlated with both the putamen BI (-8.8%/year, rho=-0.41, P=0.025) and the putamen/caudate ratio (-7.4%/year, rho=-0.51, P=0.004), but for TR no significant correlation was found (all P values >0.5). In conclusion, both FP and TR show high sensitivity in a clinically relevant setting, but FP has superior accuracy for early differential diagnosis of idiopathic parkinsonism and non-degenerative extrapyramidal disorders, as well as better sensitivity for disease follow-up.