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Automation is of paramount importance while handling radioactivity, basically for radiation protection reasons, but also to speed up procedures and improve reliability. This is especially true for the preparation of PET radiopharmaceuticals, which involve high level of starting activity and have short half-lives. From the early attempts with mechanical articulated manipulators or tele-pliers, to the modern fully automated systems giant steps have been made. Automation covers any aspect of a nuclear medicine operability, from radionuclide delivery to radiosynthesis, formulation and dose dispensing. Radionuclide transport, in liquid and gaseous form, is easy to automate, while it may be troublesome in solid form. Multi-step radiosynthetic processes can now be performed with automatic synthesis modules, using disposable or non-disposable networks of tubing/valves/vials, the former being preferred for routine preparations of clinically relevant radiopharmaceuticals, and the latter for the development of new radiolabeling methods or in case of gaseous phase chemistry. Automated dispensing systems are used to distribute the whole activity in different vials or to prepare syringes containing patient doses and are of great help in reducing radiation hazard to the personnel. Recently, also automated system capable to directly administrate the radiopharmaceuticals in patients have been developed. In parallel with their growing importance, recent advancements are broadening automation to therapeutic radiopharmaceuticals, whose preparation has largely been performed manually, to date. Although far from being considered “mature” for routine preparations, continuous findings in material sciences and sensor/electronic technology are providing “food” for further improve efficiency of radiolabeling reaction and reduce the size of automated systems, which might also have a potential economic impact. Good examples are microfluidic and automation of quality control operations.

Radiopharmaceuticals targeting the prostate-specific membrane antigen (PSMA) has become the gold standard for PET imaging of prostate cancer. [68Ga]Ga-PSMA-11 has been the forerunner but a [18F]F-PSMA ligand has been developed because of the intrinsic advantages of Fluorine-18. Fluorine-18 labelled compounds are usually prepared in centers with an on-site cyclotron. Since our center has not an on-site cyclotron, we decided to verify the feasibility of producing the experimental 18F-labelled radiopharmaceutical [18F]F-PSMA-1007 with [18F]F- from different external suppliers. A quality agreement has been signed with two different suppliers, and a well-established and correctly implemented quality assurance protocol has been followed. The [18F]F- was produced with cyclotrons, on Nb target, but with different beam energy and current. Extensive validation of the [18F]F-PSMA-1007 synthesis process has been performed. The aim of this paper was the description of all the quality documentation which allowed the submission and approval of the Investigational Medicinal Product Dossier (IMPD) to the Competent Authority, addressing the quality problems due to different external suppliers. The result indicates that no significant differences have been found between the [18F]F- from the two suppliers in terms of radionuclidic and radiochemical purity and [18F]F- impacted neither the radiochemical yield of the labelling reaction nor the quality control parameters of the IMP [18F]F-PSMA-1007. These results prove how a correct quality assurance system can overcome some Regulatory Authorities issue that may represent an obstacle to the clinical use of F-18-labelled radiopharmaceuticals without an on-site cyclotron.

Background The stability of precursors and reagents is of utmost importance for developing a robust radiolabelling method that provides high and constant radiochemical yield and radiochemical purity. While performing the QC of the [68Ga]Ga-PSMA-11 injectable solutions according to Ph. Eur. Monograph that has recently been published, a trend to the instability of the standard PSMA-11, the same used as a precursor for [68Ga]Ga-PSMA-11 radiosynthesis, has been observed. This instability led to the formation of a side product in a time-dependent manner. The formation of this compound, besides making the implementation of the Ph. Eur. analytical method more difficult, negatively influenced the radiochemical yield and the radiochemical purity by increasing gallium-68 in colloidal and ionic forms. Results The nature of the side product was investigated by adding chelators, such as EDTA, to PSMA-11 solutions and using the combination of UHPLC-HRMS. The results led to the definition of the side product structure, as natFe-PSMA-11, from the combination of the high-affinity chelator HBED-CC, present in the molecule of PSMA-11, and environmental Fe (III). Conclusions Strategies to reduce the risk of low radiolabeling yields and to increase the stability of the PSMA-11 in an aqueous solution were also discussed.

Dysfunction of the sympathetic nervous system underlies many cardiac diseases and can be assessed by molecular imaging using SPECT tracers as I-metaiodobenzylguanidine (I-MIBG). The norepinephrine analog C-meta-hydroxyephedrine (HED) has been used with PET to map the regional distribution of cardiac sympathetic neurons. Hydroxyephedrine is rapidly transported into sympathetic neurons by the norepinephrine transporter and stored in vesicles. This review describes the mechanism of action, radiosynthesis, and application of HED in the assessment of the cardiac sympathetic nervous system in heart failure, myocardial infarction, and arrhythmias. Noncardiac applications of HED in the clinical setting of sympathetic nervous system tumors and other emerging research applications are described.

Latissimus dorsi tendon transfer is currently the most commonly used transposition technique in shoulder surgery and can be performed using both an open technique—the first described—and an arthroscopic approach. This versatile transfer is indicated in cases of irreparable massive posterosuperior rotator cuff tears. This is the most common use of this tendon transfer. The authors explain what is meant by irreparability of a rotator cuff tear and what preoperative conditions can best satisfy this indication for latissimus dorsi tendon transfer. They also specify that concomitant irreparable subscapularis tear and clinically overt osteoarthritis or progressive chondropathy are contraindications to use of the technique. Surgeons have recently also started using latissimus dorsi tendon transfer in patients with irreparable subscapularis tears. In this case, the tendon fully satisfies all transfer suitability criteria and consequently probably represents its most elective indication. Indeed, in addition to improving articular function, it also helps to stabilise the joint against the progressive anteroinferior instability caused by the tear.

In our surgical technique the patient is placed in lateral decubitus position. After the diagnostic and preparatory phase carried out with arthroscopy, we proceed to harvest the tendon graft and strengthen it with wrapping sutures. We believe both of these steps to be fundamental for avoiding surgical complications during the next steps. In order to prevent iatrogenic lesions and keep the traction sutures from intertwining, we used two rubber tubes to facilitate the passage of the tendon graft into the joint. We place the tendon in an anterior–superior–lateral position relative to the humeral head.

The Authors describe their arthroscopic technique for latissimus dorsi tendon transfer as treatment for irreparable subscapularis tears. This technique can be standardized by following precise steps and the Authors describe how to follow the fundamental steps and a number of measures to be used to avoid complications. They conclude by describing the advantages of this arthroscopic technique over the tried-and-tested classic open technique.

Positron emission tomography (PET) is an imaging technology developed to use compounds labelled with positron-emitting radioisotopes as molecular probes to image and measure biochemical processes of mammalian biology in vivo. Since this area is rapidly developing, the demand for rapid synthetic methods for radiolabelling the molecule of interest is one of the main challenges for the radiochemists. This chapter will provide information about the most common radiolabelling strategies as well as the more recent developments in the synthesis of PET radiopharmaceuticals labelled with fluorine-18, carbon-11, nitrogen-13 and oxygen-15. Since gallium-68 has gained enormous importance in radiopharmacy in the last 10 years, a chapter will highlight the important role of radiolabelling with gallium-68 in clinical radiopharmacy.

PET radiopharmaceuticals are unique medicinal formulations administered to patients for diagnostic purposes in nuclear medicine. Quality control of these radiopharmaceuticals is important to assure the safety of the product before the release for clinical use. For this reason, efficient and quick tests have been adopted to check the quality of radiopharmaceutical preparations and specific procedures have been published in each country or regions such as found in the European Pharmacopoeia (EP), United States Pharmacopeia, and British Pharmacopoeia. In this chapter the parameters, the analytical techniques and the validation of analytical methods commonly employed in the quality control testing of PET radiopharmaceuticals are reported. Specific sections about the quality control of 18F, 11C, and 68Ga radiopharmaceuticals according to EP monographs are also provided as example for the routine testing of these preparations.

The introduction of 68 Ga labelled tracers has changed the diagnostic approach to neuroendocrine tumours and the availability of a reliable, long-lived 68 Ge/ 68 Ga generator has been at the bases of the development of 68 Ga radiopharmacy. The huge increase in clinical demand, the impact of regulatory issues and a careful radioprotection of the operators have boosted for extensive automation of the production process. The development of automated systems for 68 Ga radiochemistry, different engineering and software strategies and post-processing of the eluate were discussed along with impact of automation with regulations.

The aim of this study was to synthesize and preclinically evaluate anSeveral conditions for the labeling ofQuantitative labeling yields could be achieved with97 % radiochemical purity. The

Management of first-time anterior shoulder dislocation remains controversial and depends on many factors: the natural course of dislocation, the athlete’s age, the type of sports (contact-collision, noncontact and overhead sports), the type of injury and timing of injury in relation to competitive season.

The widely used Monte Carlo simulation code FLUKA has been utilized to prototype a solid target for the production of 89Zr by irradiation of a metallic 89Y target foil in a 16.5 MeV proton biomedical cyclotron, through the reaction 89Y(p, n)89Zr. Simulations were performed with and without an Al energy degrader. In the setup of the geometry of the target, state of the art support tools, like SimpleGeo, were used for accurate, detailed modeling. The results permitted a quick assessment of all possible radionuclidic contaminants and confirmed that the use of an energy degrader avoids production of the most important impurity, 88Zr. The estimated value for the activity produced in one hour of irradiation at 20 μA is 384±42 MBq; this is encouraging, indicating possible production of clinically significant amounts of activity with the relatively simple target setup adopted. Initial experimental tests gave results in excellent agreement with simulations, confirming the usefulness and accuracy of FLUKA as a tool for the design and optimization of targets for the production of PET radionuclides.

The radionuclide89Zr (T1/2=78.4ߙh) is particularly attractive for in vivo assessment of biochemical proesses characterized by biological half times in the order of several hours. In the present study we assessed the feasibility of89Zr productionviathe89Y(p,n)89Zr reaction. Irradiation tests were performed using a 16.5ߙMeV GE-PETtrace cyclotron. High purity (>99.9%) yttrium metallic foils (0.15ߙmm) were irradiated in a solid target station developed in our Institution. The literature cross section data of all the nuclear reactions possible in the energy range of interest were carefully studied to optimize the irradiation parameters. The irradiated target was dissolved in 1ߙN HCl and the activity of the sample was measured in a CRC-15 PET dose calibrator, setting different values for the calibration factor. The sample activity was then measured usin g a calibrated HPGe gamma ray detector. A comparison of the activity measurements allowed the evaluation of the calibration factor for the Capintec CRC-15 PET; for a 3ߙml syringe geometry, it was found 739±60. Saturation yields of89Zr were found to be 1150±110ߙMBq/μA for a single 0.15ߙmm thick disc irradiation (Ep=12.6→11.2ߙMeV) and 2400±220ߙMBq/μA for irradiation of two discs of total thickness 0.3ߙmm (Ep=12.6→9.5MeV). Total produced activities in the range of 200–400ߙMBq (according to target thickness) were repeatedly and safely obtained by 60ߙmin bombardments at 20ߙμA. Analysis of gamma ray spectra of all the samples showed a very high radionuclidic purity (>99.9995%).

Ozone produced from radiolytic processes was investigated as a possible health hazard in the working environment at the University Hospital “S.Orsola—Malpighi” PET facility. Intense radiation fields can generate ozone, known to be the most toxic gas produced by ionizing radiation around a particle accelerator. To evaluate ozone concentration in air, two different measurement campaigns were conducted with passive diffusion detectors. Comparison of the results with the concentration limits recommended by American Conference of Governmental Industrial Hygienists (ACGIH) demonstrated that ozone poses no health hazard to workers around a biomedical cyclotron.

AIM: To assess the utility of (11)C-choline PET/CT in the restaging of prostate cancer (PC) patients who showed a single finding on bone scintigraphy (BS) that was classified as equivocal or suspected for metastatic lesion. MATERIALS AND METHODS: A total of 25 PC patients with biochemical failure (mean PSA value 11.1 ng/mL; median value 6.3 ng/mL; range 0.2-37.7 ng/mL) after primary treatment were included in this retrospective study. All of them showed a single lesion on BS reported as suspected for metastatic lesion or as equivocal finding. Patients underwent (11)C-choline PET/CT within 1-4 months from BS. Validation was established by follow-up for at least 6 months. RESULTS: On the basis of biopsy confirmation and/or 6-month follow-up, 22 of 25 patients were classified as positive for the presence of metastatic bone lesions: 13 with a single lesion and 9 with multiple lesions. (11)C-choline PET/CT was positive in 19/25 patients and, on a lesion basis, it showed 50 positive findings. BS results were confirmed in 8/25 (32%) patients. (11)C-choline PET/CT detected multiple sites of relapse in 11/25 (44%) patients: in 2/11, a single bone lesion associated with other extraosseous sites of relapse; in 6/11, multiple bone lesions; in 3/11, multiple bone lesions and other extraosseous localizations. Finally, 6/25 patients were negative on (11)C-choline PET/CT. In 3/6 patients, an osteoblastic lesion was seen on CT attenuation correction images (PET false negative; BS true positive), while in 3/6 patients only findings suggestive of the presence of degenerative disease were found (PET true negative; BS false positive). On a patient basis, (11)C-choline PET/CT showed a diagnostic sensitivity of 86% (19/22) and a specificity of 100% (19/19). CONCLUSIONS: In our study, (11)C-choline PET/CT detected unknown lesions in 11/25 patients. Patients with a single equivocal finding on BS could have important additional information from (11)C-choline PET/CT study, especially in the detection of additional metastases, to choose an appropriate treatment

The in vivo evaluation of three modified polyethylene glycol (PEG)-anilinoquinazoline derivatives labeled with (124)I, (18)F, and (11)C as potential positron emission tomography (PET) bioprobes for visualizing epidermal growth factor receptor (EGFR) in cancer using small animal PET. PROCEDURES: Xenograft mice with the human glioblastoma cell lines U138MG (lacking EGFR expression) and U87MG.wtEGFR (transfected with an overexpressing human wild-type EGFR gene) were used. Static and dynamic PET imaging was conducted for all three PEGylated compounds. Tumor necrosis, microvessel density, and EGFR levels were evaluated by histopathology and enzyme-linked immunosorbent assay. RESULTS: Nineteen animal models were generated (two U138MG, three U87MG, 14 with both U138MG and U87MG bilateral masses). In static images, a slight increase in tracer uptake was observed in tumors, but in general, there was no retention of tracer uptake over time and no difference in uptake between U138MG and U87MG masses. In addition, no significant uptake was demonstrated in dynamic scans of the (18)F-PEG tracer. No necrosis was present except in four animals. MVD was 9.6 and 48 microvessels/×400 field in the U138GM and U87GM masses, respectively (p = 0.00008). Similarly, the microvessel grades were generally higher in the U87GM group (p = 0.002). Total EGFR amount was higher in U87MG than U138MG masses (p = 0.001), but the ratio of activated (pY1068) to total EGFR did not differ (p = 0.95). CONCLUSIONS: PEGylated tracers labeled with (11)C, (124)I, and (18)F showed no significant difference in uptake between U138MG and U87MG glioblastoma xenograft mice. The tracer binding with EGFR could be influenced by activation of the tyrosine kinase portion of the receptor which was similar in U138MG and U87MG. Despite these results, these tracers should be investigated in animal models with mutant EGFR genes to determine whether aberrant receptor function plays a role in tumor uptake

Quantitative analysis of positron emission tomography (PET) dynamic images allows to estimate physiological parameters such as glucose metabolic rate (GMR), perfusion, and cardiac output (CO). However, several physical effects such as photon attenuation, scatter and partial volume can reduce the accuracy of parameter estimation. The main goal of this work was to improve small animal PET image quality by introducing system point spread function (PSF) in the reconstruction scheme and to evaluate the effect of partial volume correction (PVC) on physiological parameter estimation. Images reconstructed respectively using constant and spatially variant (SV) PSFs and no PSF modeling was compared. The proposed algorithms were tested on simulated and real phantoms and mice images. Results show that the SV-PSF-based reconstruction method provides a significant contrast improvement of small animals PET cardiac images and, thus, the effects of PVC on physiological parameters were evaluated using such algorithm. Simulations show that the proposed PVC method reduces errors with respect to the true values for parametric images of GMR and perfusion. A reduction of CO percentage error with respect to the original value was also obtained using the SF-PSF approach. In conclusion, SV-PSF reconstruction method provides a more accurate estimation of several physiological parameters obtained from a dynamic PET scan.

[((11))C]labelled radiopharmaceuticals as N-[(11)C]methyl-choline ([(11)C]choline), l-(S-methyl-[(11)C])methionine ([(11)C]methionine) and [(11)C]acetate have gained increasing importance in clinical PET and for the routine production of these radiopharmaceuticals, simple and reliable modules are needed to produce clinically relevant radioactivity. On the other hand, flexible devices are needed not only for the routine synthesis but also for more complex applications as the development of new tracers. The aim of this work was the adaptation of an Eckert Ziegler modular system for easy routine synthesis of [(11)C]choline, [(11)C]methionine and [(11)C]acetate using components that account for straightforward scaling up and upgrades.

In this paper we describe test methods useful to evaluate the performance of Ge/ Ga generators and to assess radionuclidic purity of the eluates. In our tests on the elution profile of the generator, we found that less than 8.0 ml are sufficient to recover > 98 % of the activity. Elution yield was conforming the manufacturer specifications, being initially > 85 % and still > 64 % after 7 months of use. 68Ge breakthrough in the eluates was limited; even if radionuclidic purity was > 99.99 % , further analyses, in addition to physical tests, is recommended in order to assess chemical impurities that could determine interferences in labelling procedures.

Central nervous system (CNS) malignant tumors are usually treated with different combinations of surgery, radiotherapy and chemotherapy to achieve a radical treatment. After therapy, conventional imaging procedures (CT and MR) are useful to detect disease relapse but a correct differential diagnosis in presence post-surgical fibrosis, radionecrosis or oedema (benign conditions) may sometime be difficult. CNS shows physiologically an intense uptake of FDG and consequently, small and/or hypo/isometabolic malignant lesions are very difficult to detect, as they may be masked by the hypermetabolic surrounding tissue. 11C-Methionine is a radiolabeled aminoacid that physiologically do not accumulate into the brain, nor in case of benign conditions such as fibrosis, necrosis or oedema. On the other side, malignant lesions (although low grade) present an increased 11C-Methionine uptake due to an increased proteic metabolism and vascular permeability. Therefore 11CMethionine has optimal tumor-to-background ratio, making this radiotracer very useful to study CNS malignant tumors. The most appropriate indication for 11C-Methionine PET is the presence of non conclusive conventional imaging procedures, not allowing to discriminate between benign conditions and disease relapse. Other applications of 11C-Methionine PET are the definition of the radiotherapy field, the localization of the most metabolic area inside a mass to guide the biopsy and the early evaluation of radiotherapy effect, but all these applications are marginal and not yet validated.

N-[11C]methyl-choline ([11C]choline) and L-(S-methyl-[11C])methionine ([11C]methionine) are PET radiopharmaceuticals which have gained interest as oncological tracers. The increasing demand of these radiopharmaceuticals needs robust methods of synthesis with high and reproducible yield which provide enough activity for multiple patient administration in a short synthesis time.Different synthetic approaches have been described in the literature but exhaustive reports on performance and reliability of different methods have not been described yet.In the present study, we demonstrated the reliability and reproducibility of the solid-phase [11C]methylation method for the synthesis of [11C]choline and [11C]methionine as a suitable tool for the routine clinical use.

In this paper, radionuclidic impurities generated during the bombardment of [18 O]water in the routine production of 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) were studied. In order to assess such impurities and the efficacy of purification methods through the different steps of the synthesis, samples of the target filters, purification columns, [18 O]water recovered after the synthesis, and the final solution was collected and their activities measured and analyzed by means of a gamma-ray spectrometry system. The data demonstrated that purification methods adopted for the synthesis provide the [18F]FDG radionuclidically pure, as requested by the EU Pharmacopeia.

In recent years, a new PET compound (anti-3-(18)F-FACBC or (18)F-fluciclovine) was tested for the detection of prostate cancer relapse. Despite very promising results, only preliminary data were available with regard to the comparison to (11)C-choline. The aim of this study was to compare the detection rate of (18)F-FACBC and (11)C-choline in patients presenting a biochemical relapse.Fifty patients radically treated for prostate cancer and presenting with rising prostate-specific antigen (PSA) levels were consecutively and prospectively enrolled. All the patients were out of hormonal therapy and underwent both (11)C-choline PET/CT and (18)F-fluciclovine PET/CT within 1 week. The results were compared in terms of detection rate on a patient and lesion basis. Furthermore, a more detailed analysis regarding local, lymph node, and bone relapse was performed.On a patient-based analysis, (18)F-fluciclovine detection turned out to be significantly superior to (11)C-choline (P0.000001). This result was also true on lesion, lymph node, bone lesion, and local relapse analysis (P0.0001 in all the cases). There was no significant difference in terms of target to background of positive lesions between (11)C-choline and (18)F-fluciclovine. When the patients were divided into groups with different PSA levels, (18)F-fluciclovine had a superior detection rate for low, intermediate, and high PSA levels.In our experimental conditions, (18)F-fluciclovine provided a statistically significant better performance in terms of lesion detection rate as compared with (11)C-choline. However, more studies are required to evaluate the clinical significance of these results in terms of sensitivity, specificity, and accuracy.

Purpose: We assessed the rate of detection rate of recurrent prostate cancer by PET/CT using anti-3-18F-FACBC, a new synthetic amino acid, in comparison to that using 11C-choline as part of an ongoing prospective single-centre study. Methods: Included in the study were 15 patients with biochemical relapse after initial radical treatment of prostate cancer. All the patients underwent anti-3-18F-FACBC PET/CT and 11C-choline PET/CT within a 7-day period. The detection rates using the two compounds were determined and the target–to-background ratios (TBR) of each lesion are reported. Results: No adverse reactions to anti-3-18F-FACBC PET/CT were noted. On a patient basis, 11C-choline PET/CT was positive in 3 patients and negative in 12 (detection rate 20 %), and anti-3-18F-FACBC PET/CT was positive in 6 patients and negative in 9 (detection rate 40 %). On a lesion basis, 11C-choline detected 6 lesions (4 bone, 1 lymph node, 1 local relapse), and anti-3-18F-FACBC detected 11 lesions (5 bone, 5 lymph node, 1 local relapse). All 11C-choline-positive lesions were also identified by anti-3-18F-FACBC PET/CT. The TBR of anti-3-18F-FACBC was greater than that of 11C-choline in 8/11 lesions, as were image quality and contrast. Conclusion: Our preliminary results indicate that anti-3-18F-FACBC may be superior to 11C-choline for the identification of disease recurrence in the setting of biochemical failure. Further studies are required to assess efficacy of anti-3-18F-FACBC in a larger series of prostate cancer patients.

Several lines of evidence suggest that novel pharmacological approaches aimed at converting white adipose tissue (WAT) into brown adipose tissue (BAT) may represent an effective therapeutic strategy for obesity and related disorders. ((18))F-fluorodeoxyglucose ((18)F-FDG) is the only positron emission tomography (PET) tracer commonly used to study BAT function, and so far no functional tools have been described to investigate in vivo white-to-brown fat conversion. In this report, we show that the PET tracer (11)C-meta-hydroxyephedrine ((11)C-MHED, a norepinephrine analogue) is a useful tool to investigate the sympathetic nervous system (SNS) activity in BAT of lean and dietary obese mice. Moreover, we demonstrate that (11)C-MHED is a specific marker of the SNS-mediated thermogenesis in typical BAT depots, and that this tracer can detect in vivo WAT to BAT conversion.

Introduction: Cardiac resynchronization therapy (CRT) is an accepted treatment in patients with end-stage heart failure. PET permits the absolute quantification of global and regional homogeneity in cardiac sympathetic innervation. We evaluated the variation of cardiac adrenergic activity in patients with idiopathic heart failure (IHF) disease (NYHA III-IV) after CRT using 11C-hydroxyephedrine (HED) PET/CT. Methods: Ten IHF patients (mean age = 68; range = 55-81; average left ventricular ejection fraction 26. ±. 4%) implanted with a resynchronization device underwent three HED PET/CT studies: PET 1 one week after inactive device implantation; PET 2, one week after PET 1 under stimulated rhythm; PET 3, at 3 months under active CRT. A dedicated software (PMOD 3.4 version) was used to estimate global and regional cardiac uptake of HED through 17 segment polar maps. Results: At baseline, HED uptake was heterogeneously distributed throughout the left ventricle with a variation coefficient of 18. ±. 5%. This variable markedly decreased after three months CRT (12. ±. 5%, p.

Objective: The aim of this study was to evaluate the rate of postactinic inflammatory alterations that could lead to false-positive results in FDG-PET images, in a group of lymphoma patients studied with positron emission tomography (PET) early after the end of radiation therapy. Materials and methods: Sixteen (16) consecutive patients were referred to our center for malignant lymphoma; 14 of 16 patients had a mediastinal bulky mass at diagnosis. Each patient underwent chemotherapy and then radiotherapy (RT): for clinical reasons, shortly after RT (range, 25–56 days; mean, 38.7 days) a FDG PET scan was required to evaluate the effect of therapy. We intravenously injected 370 MBq of 18F-FDG, and after 60–90 minutes we recorded images. Results: Despite a relatively short time after RT, there was no pathological tracer uptake in 13 of 16 patients. In 3 cases, a mild increase in FDG uptake was observed, but no findings which would lead to a false-positive diagnosis. In 2 of 3 cases, postactinic pneumopathy wa...

Objective: This study was done to evaluate left ventricular structure and function among pregnant patients with preeclampsia and compare them with those of normotensive pregnant and nonpregnant subjects. It also tested the hypothesis that abnormalities in left ventricular structure and function are associated with elevated plasma levels of natriuretic peptides. Study Design: The study compared 75 pregnant women (n = 40 with preeclampsia; n=35 normotensive pregnant women) and 10 nonpregnant normotensive control subjects undergoing an echocardiographic and biohumoral (renin activity and aldosterone, atrial natriuretic peptide, and brain natriuretic peptide concentrations) evaluation. The statistical analysis was carried out by analysis of variance, and significance was set at P Results: Comparison of pregnant patients with preeclampsia versus both normotensive pregnant women and nonpregnant women showed significant increases in left ventricular mass and left ventricular endsystolic and end-diastolic volumes and significant reductions in left ventricular ejection fraction and percentage of fractional shortening. These changes coincided with increases in plasma levels of atrial natriuretic peptide and brain natriuretic peptide that were linearly related to the left ventricular structural and functional changes observed in patients with preeclampsia. Conclusion: Pregnant patients with preeclampsia showed adaptation to the increase in systemic blood pressure, with significant modification of left ventricular structure and function related to the plasma levels of both atrial natriuretic peptide and brain natriuretic peptide. A simple evaluation of plasma natriuretic peptide concentrations could help to discriminate patients with preeclampsia who have a condition of mild left ventricular overload. (Am J Obstet Gynecol 2000;183:140-7.)

Background: Rectal treatment with mesalazine enemas is the first-line therapy for distal ulcerative colitis. In order to improve the benefits of rectal therapy, a new 60 mL 5-ASA rectal gel enema preparation has been developed using a device which excludes direct contact of the inert propellant gas with the active drug. The purpose of the present study was to assess by scintigraphy the colonic distribution of this new mesalazine rectal gel enema. Methods: Twelve patients with active ulcerative colitis were administered 4 g of the mesalazine rectal enema labelled with 100 MBq technetium sulphur colloid (99mTc-SC). Anterior scans of the abdomen were acquired at intervals for 4 h. Scans were analysed to evaluate the extent of retrograde flow and homogeneity of distribution of the radiolabelled enema in the rectum, sigmoid, descending and transverse colon. In addition, plasma levels of 5-ASA and Ac-5-ASA were measured for 6 h. Results: All patients retained the entire rectal gel throughout the course of the study without reporting adverse events. In 11 out of 12 patients (92%) the gel had spread homogeneously beyond the sigmoid colon and had reached the upper limit of disease in all cases. The maximum spread (splenic flexure) was observed in 6 out of 12 patients (50%) within the first 2 h. The systemic absorption of mesalazine and its metabolite Ac-5-ASA was low. Conclusions: The new mesalazine enema represents an adequate alternative and a further technological improvement in the topical treatment of distal ulcerative colitis.

To investigate the involvement of endogenous opioids in acute increases in blood pressure and their functional relationship with atrial natriuretic factor and endothelin-1, we assessed plasma levels of β-endorphin, met-enkephalin, dynorphin B, catecholamines, atrial natriuretic factor, and endothelin-1 before and after administration of the opioid antagonist naloxone hydrochloride (8 mg IV) in 28 hypertensive patients with a stress-induced acute increase in blood pressure. Ten patients with established mild or moderate essential hypertension and 10 normotensive subjects served as control groups. Opioids, atrial natriuretic factor, and endothelin-1 were radioimmunoassayed after chromatographic preextraction; catecholamines were determined by high-performance liquid chromatography with electrochemical detection. Patients with an acute increase in blood pressure (systolic, 203.2±2.2 mm Hg; diastolic, 108.4±1.3) had plasma opioid, catecholamine, and atrial natriuretic factor levels significantly ( P P

Healthy subjects were classified according to their percent increase in systolic blood pressure (SBP) after mental arithmetic test (MAT) as low (delta SBP 9.3-15.1%, n = 15) and high (delta SBP 35.1-45.4%, n = 15) responders. During MAT, low responders showed significantly (p < 0.01) increased plasma levels of beta-endorphin, cortisol, catecholamines, and atrial natriuretic factor (ANF) and decreased levels of endothelin-1, whereas high responders showed increased (p < 0.01) levels of Metenkephalin, dynorphin B, and catecholamines. Pretreatment with naloxone hydrochloride enhanced (p < 0.01) SBP, heart rate, noradrenaline, cortisol, and endothelin-1 levels, and reduced (p < 0.01) ANF in low responders in response to MAT, whereas it decreased (p < 0.01) hemodynamic parameters, noradrenaline, and endothelin-1 in high responders. The individual differences in hemodynamic and endocrine responses to MAT may depend on a different activation of the endogenous opioid system.

Negli ultimi anni il rapido sviluppo delle biotecnologie ha permesso di acquisire importanti conoscenze sulle basi molecolari che regolano il funzionamento normale o patologico di organismi di diversa complessita. Dal punto di vista della medicina, cio ha rappresentato la base per l’identificazione di approcci terapeutici innovativi fondati sul concetto di medicina molecolare e di terapia personalizzata. A loro volta, medicina molecolare e terapia personalizzata hanno determinato un notevole input e ampia diffusione delle metodiche di imaging biomedico sia in campo clinico sia, soprattutto negli ultimi anni, nel settore preclinico.

It has been shown that in vitro calcium channel blockers may regulate insulin secretion, and in vivo studies have demonstrated that they can reduce the degree of hyperinsulinemia and ameliorate the insulin-resistant state in subjects (particularly men) with obesity and hypertension. It is also commonly accepted that hyperinsulinemia may be an important factor responsible for the development of hyperandrogenism in obese women with polycystic ovarian syndrome (PCOS). We, therefore, investigated whether the administration of nitrendipine, a widely used calcium channel blocker, may improve both insulin levels and hyperandrogenism in a group of seven insulin-resistant hyperinsulinemic women with obesity and PCOS. They were treated for 7-8 days with oral nitrendipine (10 mg, twice daily) or placebo using a double blind, cross-over design. Before and after treatment, blood samples were obtained for androgen and sex hormone-binding globulin determinations, and an oral glucose tolerance test was performed, measuring glucose and insulin. Both nitrendipine and placebo failed to decrease basal and stimulated insulin levels. Moreover, no significant variations in testosterone, dehydroepiandrosterone sulfate, or sex hormone-binding globulin concentrations were observed after either treatment. Therefore, these data fail to support previous suggestions that calcium channel blockers may play a role in the treatment of hyperandrogenism and hyperinsulinemia in obese women with PCOS.

There are no studies in vivo on the effects of insulin on androgens and sex hormone-binding globulin (SHBG) in men. We, therefore, investigated the effects of insulin suppression on testosterone and SHBG in two groups of eight nondiabetic adult obese men and six healthy normal weight men who underwent diazoxide treatment (100 mg, three times daily) for 7 days. Blood samples for hormone determination were obtained before the subjects had been selected for the study, immediately before diazoxide administration, and on the last day of treatment. A 24-h oral glucose tolerance test was also performed for glucose, insulin, and C-peptide determinations before and on the last day of treatment. Only one subject experienced significant side-effects, and no significant changes in mean body weight were found during the treatment. Diazoxide administration worsened glucose tolerance in several subjects and reduced fasting and glucose-stimulated insulin levels by approximately 50% in both control and obese subjects. No significant difference was present between historical and pretreatment hormone values in either group. Moreover, there were no differences in pretreatment gonadotropin and SHBG concentrations between the two groups, whereas testosterone (free and total) levels were lower in the obese than in the control subjects. After diazoxide administration, testosterone (free and total) decreased slightly, but significantly, whereas LH and SHBG significantly increased in both groups. Diazoxide treatment increased estradiol levels in controls, but not in obese men. In conclusion, these results indicate that in vivo, insulin is capable of stimulating testosterone production and, simultaneously, of inhibiting SHBG concentrations in both normal weight and obese men.

In the last years (68)Ga has got into the focus of researchers and clinicians especially for radio-labeling of biomolecules; an important characteristic of this positron emitting isotope is its availability via the (68)Ge/(68)Ga generator system: the long-lived (68)Ge (t1/2=270.8 d) produces the short-lived (68)Ga (t1/2=67.63 min) which decays to stable (68)Zn. (68)Ge breakthrough compromises (68)Ga radionuclidic purity, while (68)Zn might affect the specific activity of the radiopharmaceutical. In this paper we investigated the weight of these impurities in (68)Ga-DOTANOC synthesis. (65)Zn (t1/2=244.26d; decay mode: EC 98.3%, β(+) 1.7%) was used as a radiotracer of stable (68)Zn; samples of the purification columns, wastes and product were recovered and measured with a calibrated HPGe gamma-ray spectrometry system. The results showed that (68)Zn competes with (68)Ga in labeling DOTANOC with a (95±2)% labeling yield; they also proved the effectiveness of the STRATA X-C cationic post-processing of the generator eluate in lowering the amount of this impurity to less than 1%. Moreover this approach, along with the purification of the final product through a STRATA X cartridge, effectively removes (68)Ge breakthrough providing a (68)Ga-DOTANOC radionuclidic purity of (99.9999986±0.0000006)%, superior to 99.9% required by the Pharmacopoeia Monograph on (68)Ga Edotreotide injection.

The renaissance of (68)Ga radiopharmacy has led to great advances in automation technology. The availability of a highly efficient, reliable, long-lived (68)Ge/(68)Ga generator system along with a well-established coordination chemistry based on bifunctional chelating agents have been the bases of this development in (68)Ga radiopharmacy. Syntheses of (68)Ga peptides were originally performed by manual or semiautomated systems, but increasing clinical demand, radioprotection, and regulatory issues have driven extensive automation of their production process. Several automated systems, based on different post-processing of the (68)Ga generator eluate, on different engineering, and on fixed tubing or disposable cassette approaches, have been developed and are discussed in this chapter. Since automatic systems for preparation of radiopharmaceuticals should comply with qualification and validation protocols established by regulations such as current Good Manufacturing Practices (cGMP) and local regulations, some regulatory issues and the more relevant qualification protocols are also discussed.