A kinetics-based approach to amyloid PET semi-quantification.

PURPOSE: To develop and validate a semi-quantification method (time-delayed ratio, TDr) applied to amyloid PET scans, based on tracer kinetics information. METHODS: The TDr method requires two static scans per subject: one early (~ 0-10 min after the injection) and one late (typically 50-70 min or 90-100 min after the injection, depending on the tracer). High perfusion regions are delineated on the early scan and applied onto the late scan. A SUVr-like ratio is calculated between the average intensities in the high perfusion regions and the late scan hotspot. TDr was applied to a naturalistic multicenter dataset of 143 subjects acquired with [18F]florbetapir. TDr values are compared to visual evaluation, cortical-cerebellar SUVr, and to the geometrical semi-quantification method ELBA. All three methods are gauged versus the heterogeneity of the dataset. RESULTS: TDr shows excellent agreement with respect to the binary visual assessment (AUC = 0.99) and significantly correlates with both validated semi-quantification methods, reaching a Pearson correlation coefficient of 0.86 with respect to ELBA. CONCLUSIONS: TDr is an alternative approach to previously validated ones (SUVr and ELBA). It requires minimal image processing; it is independent on predefined regions of interest and does not require MR registration. Besides, it takes advantage on the availability of early scans which are becoming common practice while imposing a negligible added patient discomfort.

Precise control of thermal conductivity at the nanoscale through individual phonon-scattering barriers.

The ability to precisely control the thermal conductivity (kappa) of a material is fundamental in the development of on-chip heat management or energy conversion applications. Nanostructuring permits a marked reduction of kappa of single-crystalline materials, as recently demonstrated for silicon nanowires. However, silicon-based nanostructured materials with extremely low kappa are not limited to nanowires. By engineering a set of individual phonon-scattering nanodot barriers we have accurately tailored the thermal conductivity of a single-crystalline SiGe material in spatially defined regions as short as approximately 15 nm. Single-barrier thermal resistances between 2 and 4 x 10(-9) m(2) K W(-1) were attained, resulting in a room-temperature kappa down to about 0.9 W m(-1) K(-1), in multilayered structures with as little as five barriers. Such low thermal conductivity is compatible with a totally diffuse mismatch model for the barriers, and it is well below the amorphous limit. The results are in agreement with atomistic Green's function simulations.

FDG-PET in the assessment of patients with follicular lymphoma treated by ibritumomab tiuxetan Y 90: multicentric study.

BACKGROUND: The aim of this study is the 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) evaluation following radioimmunotherapy (RIT) with ibritumomab tiuxetan Y 90 in patients with non-Hodgkin's follicular lymphoma (FL). MATERIALS AND METHODS: We retrospectively analyzed data from 59 relapsed or refractory FL patients treated with ibritumomab tiuxetan Y 90 in four different PET centers who had a PET scan carried out before and after RIT. Possible predictive factors of progression-free survival (PFS) were studied through univariate and multivariate analysis. RESULTS: The post-RIT PET documented 45.8% complete responders (CR), 25.4% partial responders (PR) and 28.8% nonresponders [stable disease + progressive disease], with an overall survival of 71.2% (range 59.5%-90.9%). With a median follow-up period of 23 months, the univariate analysis documented a statistically significant relation between disease extent before RIT and response to treatment with respect to PFS (P = 0.015), while all the other prognostic factors showed no significant correlation. When carrying out the multivariate analysis, post-RIT PET resulted as the lonely independent predictor of PFS (P < 0.00001). CONCLUSIONS: RIT is an effective therapy in FL patients, as confirmed in our study too. Disease extension before treatment and response to RIT, as assessed by FDG-PET, result as main predictors of PFS, with the post-RIT PET result being the only independent predictive factor.

Activated macrophages are the main inflammatory cell in COVID-19 interstitial pneumonia infiltrates. Is it possible to show their metabolic activity and thus the grade of inflammatory burden with 18F-Fluorocholine PET/CT?

The recent outbreak of Covid-19 has represented a major challenge for the countries affected by the disease, not only in terms of loss of human life, economic downturn, and constraint on individual freedom, but also for the great pressure on the national health systems and hospitals. The 380 kDa virus has been a perfect storm, especially for those national health systems used to working with limited resources and high intensity rhythms, such as Italy. For the first time in the new century, a virtually unknown fast-spreading disease has caused a public health emergency thus forcing most countries to deal with an insurmountable logistic gap. Hence, every branch of Medicine, even though not directly involved in the treatment, has been called upon to provide its contribution to resolve the crisis. It is now becoming more apparent that Covid-19 is not solely a lung disease, but a complex systemic disease involving several organs and systems. This is due to an abnormal inflammatory response which eventually leads to multisystemic coagulopathy which mainly, but not uniquely, targets the lungs. Although the pathophysiology of this syndrome is still not fully understood, macrophages and their immune complex system seem to play a key role. It is not yet clear why some patients develop the violent immune response which results in pneumonitis while others do not. There are clues indicating that the systemic hyper-inflammation defined as macrophage activation syndrome (MAS), or cytokine storm, requires an increase in choline consumption to synthesize phosphatidylcholine and stimulate phagocytosis, organelle biogenesis, secretory functions, and endocytosis. 18F-Fluorocholine is a synthetic analog of the naturally occurring choline normally used for PET/CT imaging of prostate cancer patients. 18F-Fluorocholine could image and quantify the macrophage activity in pulmonary interstitial infiltrates of Covid-19 pneumonia. If the hypothesis is confirmed experimentally, 18F-Fluorocholine PET/CT could be used to in vivo image and quantify the degree of lung inflammation and potentially stratify the gravity of this disease.

Assessment of mediastinal involvement in lung cancer with technetium-99m-sestamibi SPECT.

UNLABELLED: This study evaluated the clinical role of SPECT with sestamibi versus CT in the presurgical staging of lung cancer. METHODS: Forty-seven consecutive patients (44 men, 3 women; mean age 63.3 yr, range 49-82 yr) with clinical and radiological suspicion of lung cancer were enrolled in this study. Staging procedures including radiography, CT, fiberoptic bronchoscopy and sestamibi SPECT of the thorax. Radionuclide imaging was performed after intravenous injection of 740-925 MBq of sestamibi. In 36 patients a histological diagnosis was made, and these patients were evaluated for the study of mediastinal lymph node involvement. RESULTS: Mediastinal lymph node involvement was demonstrated in 11 of the 36 patients evaluated. Sestamibi SPECT correctly staged 10 of 11 patients with and 21 of 25 without mediastinal nodes, showing a diagnostic sensitivity of 91% and a specificity of 84%. Computed tomography gave 8 true-positive and 15 true-negative results, with a sensitivity of 73% and a specificity of 60%. Sestamibi SPECT results were also better than those of CT with regard to positive and negative predictive values and accuracy. CONCLUSION: The clinical role of sestamibi SPECT can be fully appreciated when the technique is used in selected patients, combined with CT or MRI, or both, to assess mediastinal involvement and avoid any invasive staging procedures.

Control of enzyme properties in supramolecular systems.

The study deals with stability and activity of enzymes in supramolecular systems. Acid phosphatase (EC 3.1.3.2) has been studied as model enzyme. The organic phase is rich in C2-C4 acetates. Didodecyldimethylammonium chloride (DD-DACl) has been mainly used as ionic surfactants. The rate of enzyme inactivation is smaller than in buffer and is less dependent on storage temperature. Specific activity of the enzyme is lowered because of a less affinity towards the substrate and of reduction of maximal velocity.

Effects of ionic and zwitterionic surfactants on the stabilization of bovine catalase.

The activity and stability of beef liver catalase have been investigated in the presence of different ionic and zwitterionic surfactants. All cationic and zwitterionic surfactants used in this work have no effect on the initial activity of catalase, but several of them allow the enzyme to retain a high residual activity for longer periods of time than those observed in the absence of any additives. However, the interactions between surfactants and catalase appear to be very peculiar, and certain zwitterionic surfactants have been found to remarkably slow down enzyme degradation, with the enzyme completely preserving its activity after several weeks at temperatures of up to 30 degrees C. This effect is probably due to an interaction between the surfactant and the intersubunit region of the protein; this interaction could stabilize the quaternary structure of the enzyme.

Influence of sulfobetaines on the stability of the Citrobacterdiversus ULA-27 beta-lactamase.

The activity and stability of beta-lactamase from Citrobacter diversus ULA-27 have been investigated in the presence of different ionic and zwitterionic surfactants. All the sulfobetaine surfactants tested allow the enzyme to retain its full activity, but the best stabilizing effect is greatly dependent on their structure. Very little variations on the monomer headgroup can significantly reduce enzyme deactivation or speed up the loss of activity with respect to buffer alone. The whole hydrophobic/hydrophilic balance on the headgroup seems to have a determining role in preserving beta-lactamase activity and structure. The presence of zwitterionic surfactants stabilizes the protein conformation toward denaturation by urea and low-temperature inactivation. Similar experiments were performed in the presence of other two zwitterionic surfactants, an amine oxide, dimethylmyristylamine oxide (DMMAO) and a carboxybetaine, cetyldimethylammonium methanecarboxylate (CB1-16). The former stabilizes the enzyme even better than the sulfobetaines, the latter quickly deactivates it. Therefore, the factors responsible for beta-lactamase stabilization are dependent not only on the zwitterionic nature of the surfactant headgroup but also specific interactions between the surfactant and the protein may be important.

The role of bone SPET study in diagnosis of single vertebral metastases.

The spine is the preferential site of metastases from several neoplasms. In the past years whole body bone scan (BS) with 99mTc-diphosphonates has been considered the first choice in detecting the skeletal involvement. However the presence of vertebral non-neoplastic pathology in oncologic patients can cause several false positive results and this increases the difficulty in defining the etiology of a focal uptake. Nowadays, technological development has provided new gamma cameras, which are able to perform tomographic acquisition (single photon emission tomography, SPET). This technique allows one to better define the anatomical location of the areas of increased uptake. In our study, 81 cancer patients, with suspected single skeletal metastases not defined by BS, were studied by SPET. The skeletal involvement was confirmed during at least 12 months follow up by means of clinical, radiological and nuclear medicine examinations. The overall malignant bone alterations were 14 while the benign ones were 67. The performances of SPET were: diagnostic sensitivity 92.8% (13/14), specificity 92.5% (62/67) positive predictive value 72.2% (13/18), negative predictive value 98.4% (62/63), accuracy 92.6% (75/81). Our conclusion is that bone SPET proved to be a very reliable tool in differentiating benign disease from metastatic involvement.

BTA-TRAK combined with urinary cytology is a reliable urinary indicator of recurrent transitional cell carcinoma (TCC) of the bladder.

This study evaluated the diagnostic accuracy of BTA-TRAK in combination with urinary cytology (UC) in the follow-up of patients with a history of transitional cell carcinoma (TCC) of the bladder. The overall sensitivity of BTA-TRAK, UC and the two tests combined for the detection of recurrences was 82.7% (48/58), 84.2% (48/57) and 91.2% (52/57), respectively. BTA and UC showed comparable sensitivity for superficial recurrences (76.7% (33/43) and 78.5% (33/42), respectively) and for invasive recurrences (100% (15/15)); when the two tests were used in combination, the sensitivity for superficial lesions increased to 88% (37/42). BTA-TRAK was more sensitive than UC for G1 recurrences (81.2% (13/16) vs. 68.7% (11/16)), and when the two tests were combined the sensitivity increased to 87.5% (14/16). The sensitivity of the combination was 100% (15/15) for G3 lesions. The differences in urinary BTA-TRAK levels between patients with recurrences and those without evidence of disease were statistically significant (Wilcoxon's test, p<0.05); among patients with recurrences BTA levels were significantly higher in the invasive and poorly differentiated subtypes. In the series of patients studied by us, BTA-TRAK combined with UC was shown to be a non-invasive, accurate test to predict TCC recurrences. Periodic measurement of BTA-TRAK combined with urinary cytology seems to provide additional information for the monitoring of patients treated for TCC; however, due to the presence of false positive and false negative results, this test cannot replace cystoscopy. In a selected group of patients it could, if combined with cytology and ultrasonography and if correctly used and interpreted, orient the timing and indication for cystoscopy.

Kinetics and mechanism of the basic hydrolysis of indomethacin and related compounds: a reevaluation.

The kinetics of the hydrolysis of indomethacin and related compounds were studied in an alkaline medium at 25 degrees. The pseudo-first-order rate constants were evaluated from log absorbance versus time plots in the ultraviolet. These compounds showed a second-order rate constant at low concentrations of hydroxide ion and a first-order rate constant at higher concentrations of hydroxide ion.

Micellar effects on the basic hydrolysis of indomethacin and related compounds.

The kinetics of hydrolysis of indomethacin and related compounds was studied in an alkaline medium at 25 degrees C in the presence of anionic (sodium dodecyl sulfate) and cationic (hexadecyltrimethylammonium bromide) surfactants. The rate-surfactant profiles for rate inhibition in the presence of sodium dodecyl sulfate and rate enhancement in the presence of hexadecyltrimethylammonium bromide were analyzed in terms of the current theory of micellar effects.

Gallium-67 as a tumor-seeking agent in lymphomas--a review.

BACKGROUND: At present 67Ga can be considered one of the most widely used viability radiotracers. There is general consensus in the literature that 67Ga has the highest clinical value in the management of lymphoma patients. METHODS: We critically discuss the role of gallium scintigraphy in lymphoma patients on the basis of the experience of the Nuclear Medicine Division at the National Cancer Institute of Milan. RESULTS AND CONCLUSIONS: The sensitivity of gallium scan is very high (80-90%) in the staging and follow-up of Hodgkin's disease, and the method is also of great importance in the follow-up of lymphoma patients. We recommend scintigraphy to study the residual mediastinal mass after treatment. Our experiences during the follow-up of 189 lymphoma patients clearly showed the superior performance of gallium scan compared to MRI in the study of the mediastinal region after treatment. Sensitivity and specificity were both very high (90% and 96.9% vs 88.7% and 89.2%, respectively). Gallium scintigraphy can also be used to study the disease-free interval, post-treatment survival, early signs of recurrence and treatment response times. Comparison of the survival curves of 33 patients with diffuse large cell Non-Hodgkin's lymphoma examined at the National Cancer Institute showed a statistically significant difference (logrank test, P = 0.0125) between patients with positive and those with negative gallium scan after 4-6 cycles of chemotherapy.

Predictive value of thyroglobulin changes for the efficacy of thyroid remnant ablation.

The aim of this case-control study was to determine the utility of the evaluation of changes in serum thyroglobulin (Tg) levels before and after 1311 diagnostic total body scan (TBS) in patients with thyroid cancer to predict the efficacy of radioiodine ablation. Among 134 consecutive patients with differentiated thyroid carcinoma (DTC) who had undergone a thyroidectomy and TBS prior to radioiodine ablation, we selected those subjects with no evidence of distant metastases and with two consecutive assessments of Tg before TBS and radioiodine ablation within a period of four weeks. With this selection procedure 27 patients (22 with papillary and five with follicular carcinomas) were included in our evaluation. The ablation therapy was considered successful when the TBS performed one year after treatment did not show any or less than 1% cervical 131I uptake, Tg levels remained below 3 ng/mL, and clinical and instrumental examinations were negative for the presence of relapses. These criteria divided the selected patients into two subsets: patients with successful radioiodine ablation and patients with residual thyroid tissue. The majority of patients with unsuccessful ablation showed an increase in serum Tg levels, while most of the patients with successful ablation showed a steady decrease in Tg concentrations. Statistical analysis evidenced that the increase in Tg levels after TBS was related to unsuccessful ablation (P > or = 0.01). By contrast, the rate of thyroid remnants with 131I uptake did not show any relationship with the outcome of ablation therapy. The group of patients with increasing Tg levels after TBS had a relative risk of 3.3 of unsuccessful ablative therapy compared to the group with stable or decreasing Tg levels. This study supports the concept that by monitoring Tg levels in patients who undergo diagnostic TBS before radioiodine ablation it is possible to obtain useful information about the efficacy of 131I therapy.

Bone lesion in a patient with transplanted liver for a metastatic carcinoid. The role of somatostatin receptor scintigraphy.

A patient who had previously undergone ileal resection and liver transplantation for a gastroenteropancreatic (GEP) tumor was evaluated with somatostatin receptor scintigraphy (SRS) using 111In-DTPA-D-Phe1-pentetreotide. Eighteen months after surgery, during follow-up procedures, conventional imaging techniques (ultrasound, computed tomography, magnetic resonance imaging) only showed a relapse in the gastropancreatic lymph nodes, while SRS demonstrated skeletal spread. This case report emphasizes the clinical impact of SRS on the management of patients affected by neuroendocrine gastroenteropancreatic tumors.

[Evaluation of omethoate and fenitrothion absorption in greenhouse workers using protective equipment in confined areas]. / Valutazione dell'assorbimento di ometoato e fenitrothion durante lavorazioni eseguite con l'uso di mezzi personali di protezione in ambienti confinati.

Sprayers and workers engaged in manual operations in a greenhouse were monitored for exposure to omethoate and fenitrothion. Urinary dialkyl phosphates (dimethyl thiophosphate and dimethyl phosphate) were used as biological index of exposure to the two chemicals. Residues of fenitrothion on foliage were measured as well as levels of fenitrothion and omethoate in air samples collected in the breathing zone (personal sampling) and in the work-place near the entrance and the end of the greenhouse (static sampling). Skin exposure was estimated from pads placed on the thorax under overalls and from hand washing liquid at the end of the workshift. Sprayers wore respiratory and skin protection during the workshift. Workers engaged in manual operations did not wear respiratory protection. Re-entry to the greenhouse was permitted 48 h after spraying. Levels of omethoate and fenitrothion in air samples, on pads and on the hands, during manual operations on ornamental plants, were very low. Urine analysis shoved no significant difference between the pre- and post-exposure samples. No significant difference was found between levels of urinary dialkyl phosphates in the control group and exposed workers. Cholinesterase activity (acetyl and butyryl) showed no significant reduction at the end of the workshift compared with baseline values.

Viscoelastic solutions formed by worm-like micelles of amine oxide surfactant.

Formation and properties of viscoelastic wormlike aqueous micellar solutions of the zwitterionic surfactant p-dodecyloxybenzyldimethylamine oxide (pDoAO) were studied. Semi-dilute aqueous solutions of pDoAO show a sharp increase in viscosity, which exceeds 160 cST for concentrations >50 mM, leading to viscoelastic solutions. Viscoelasticity relates to the surfactant charge type. In fact this viscoelastic system reverses to fluid when acid is added (pH<2), which changes the system to cationic. Under acidic conditions the system resembles solutions of the similar cationic surfactant p-dodecyloxybenzyltrimethylammonium bromide, (pDoTABr) in terms of viscosity. Properties of aqueous solutions of pDoAO were investigated by dynamic light scattering (DLS), rheology and small angle neutron scattering (SANS). Data support the idea that small micelles grow in length (wormlike or threadlike micelles) as surfactant concentration increases and viscoelastic solutions form as micelles become entangled. The micellar diameter as calculated by different techniques is about 5 nm.

¹³¹I treatment of toxic nodular goiter under combined thyrostatic-thyromimetic medication is at low risk of late hypothyroidism.

AIM: Treatment of toxic nodular goiter with ¹³¹I is a first-line therapy for hyperthyroidism. To avoid a thyrotoxic storm, ¹³¹I is usually administered after pretreatment with antithyroid drugs, with thyroid-stimulating hormone (TSH) increase and functional recruitment of inhibited normal tissue. Therefore, both autonomous nodule(s) and normal tissue are irradiated. This may be a reason for late hypothyroidism occurring in 15-25% of patients. This study aimed at assessing different pretreatment modalities with combined methymazole and triiodothyronine, achieving euthyroidism with suppressed TSH. METHODS: After diagnosis of autonomously functioning toxic nodule, patients were subjected to thyrostatic medication. Two months later, TSH was checked; if >0.5 mU/L triiodothyronine treatment was associated. After 2 more months, if the TSH level was suppressed, patients received ¹³¹I-therapy. A total of 149 patients were consecutively enrolled, 41 of whom with uninodular and 108 with multinodular goiter. They were evaluated at diagnosis, pretreatment, 3 and 6 months after therapy and at late follow-up (6.8+/-4.2 years; range: 1-22 years). RESULTS: Administered activity was calculated according to ¹³¹I uptake and gland weight. Methymazole was discontinued 6 days before treatment and T3 was maintained until administration of ¹³¹I-therapy. Euthyroidism was achieved in 88% of patients. At late follow-up, subclinical hypothyroidism was observed in 10 patients (6.7%) and overt hypothyroidism in 5 patients (3.3%). No pathological consequences or side effects of ¹³¹I-therapy were found during the 6.8+/-4.2 year follow-up period. CONCLUSION: Treatment of toxic nodular goiter with ¹³¹I-therapy, under combined thyrostatic-thyromimetic treatment is a simple, safe, well-tolerated, and effective procedure.