A preliminary study for the production of high specific activity radionuclides for nuclear medicine obtained with the isotope separation on line technique.

Radiopharmaceuticals represent a fundamental tool for nuclear medicine procedures, both for diagnostic and therapeutic purposes. The present work aims to explore the Isotope Separation On-Line (ISOL) technique for the production of carrier-free radionuclides for nuclear medicine at SPES, a nuclear physics facility under construction at INFN-LNL. Stable ion beams of strontium, yttrium and iodine were produced using the SPES test bench (Front-End) to simulate the production of 89Sr, 90Y, 125I and 131I and collected with good efficiency on suitable targets.

Cytochrome P450 and radiopharmaceutical metabolism.

Positron emission tomography (PET) is a powerful non-invasive probe to investigate human physiology. A large number of radiotracers have been studied as imaging agents, but only a few have found clinical applications in pharmacology. A potential radiopharmaceutical is designed with very specific physiochemical characteristics, but, generally, less attention is paid to its adsorption, distribution, metabolism, and excretion properties, especially metabolism. Understanding the metabolic fate of radiopharmaceutical probes is essential for an accurate analysis and interpretation of PET measurements. The inherent inability of PET to differentiate between a parent compound and its metabolites confounds the interpretation of images and may impact the identification of the pathologically induced biochemical changes under investigation. Cytochrome P450 plays a major role in mammalian xenobiotic biotransformation and many in vitro methods are available to study and predict drug metabolism. The purpose of this review is to highlight the existing in vitro techniques available to investigate the biotransformation of xenobiotics in a fashion analogous to small molecule drug discovery. The aim is to facilitate the development and validation phases of PET tracers during preclinical evaluation. Emphasis is placed also on describing how cross species comparisons are essential in establishing appropriate translational pharmacology. Procedures of analysis (tandem liquid chromatography-mass spectrometry), typically used for studying the metabolism of drugs, are proposed as quick and accurate tools for the determination of a radiopharmaceutical's metabolic stability at the tracer level.

Performance measurements of a high-spatial-resolution YAP camera.

Physical properties of a position-sensitive camera for the analysis of biodistributions of gamma- and beta-emitting radiopharmaceuticals in small animals have been studied, in order to achieve optimal operating conditions. The camera consisted of a highly segmented yttrium-aluminate perovskite (YAP) scintillator, coupled to a position-sensitive photomultiplier. The energy resolution, the detection efficiency, the spatial resolution, the spatial linearity and the count-rate linearity of the YAP camera have been determined. Images related to initial activity levels and successive biodistribution evolution in mice organs are presented as an illustration of the camera performance.

In vitro and in vivo characterization of Indium-111 and Technetium-99m labeled CCK-8 derivatives for CCK-B receptor imaging.

Cholecystokinin (CCK) receptors of the subtype B (CCK-BR) have been shown to be overexpressed in certain neuroendocrine tumors including medullary thyroid cancer. Our recent work has focused on new methods to radiolabel the CCK8 peptide with 111In or 99mTc for CCK-B receptor imaging. Derivatives of CCK8 were obtained by addition at the N-terminus in solid phase of a DTPA derivative (DTPAGlu) linked through a glycine spacer (DTPAGlu-G-CCK8) or cysteine, glycine and a diphenylphosphinopropionyl moiety (PhosGC-CCK8) for labeling with 111In and 99mTc, respectively. CCK-BR overexpressing A431 cancer cell lines were utilized to characterize in vitro properties of the two compounds as well as for generating xenografts in nude mice for in vivo characterization. Both 111In-DTPAGlu-G-CCK8 and 99mTcPhosGC-CCK8 showed similar binding affinities for CCK-BR with dissociation constants of 20-40 nM, were internalized after interaction with the receptor and displayed prolonged cellular retention times. Specific in vivo interaction with the receptor of both CCK8 analogs was observed in our animal model. 111In-DTPAGlu-G-CCK8 showed better target to non-target ratios, although it appeared to be rapidly metabolized after injection and activity cleared through the kidneys. 99mTc-PhosGC-CCK8 was more stable in vivo but showed marked hepatobiliary clearance with resulting high background activity in the bowel. The rapid clearance and lower background obtained with 111In-DTPAGlu-G-CCK8 make this a better candidate for further development.

99mTc-labeling experiments on CCK(4) by a direct method.

99mTc-labeling studies have been performed on CCK(4) fragment of cholecystokinin, starting from 99mTc-pertechnetate, by using tin(II)pyrophosphate or tin(II)gluconate as reducing agents, together with NaBH(4) acting as a stabilizing agent of tin(II). Gluconate has been used as exchange ligand in the carrier added experiments and in the syntheses of 99Tc-CCK(4) and Re-CCK(4) complexes to be able to reproduce at macroscopic level the same chemical reactions occurring at non carrier added conditions. 99mTc-labeling yields higher than 95% have been achieved depending on Sn(II) concentration, CCK(4)/gluconate ratio, reaction time and applied temperature. The species produced with 99mTc, 99Tc, and cold rhenium nuclides have been compared by means of HPLC measurements, which showed similar retention times and thus probably the same species in the three situations.

18F-labeled radiopharmaceuticals for PET in oncology, excluding FDG.

This article reviews possible use of (18)F-labelled radiopharmaceuticals in oncology with positron emission tomography. The characteristics of various (18)F-labelled compounds are proteins and peptides, those that bind to. receptors, agents to assess hypoxia, and agents to evaluate gene therapy are highlighted. Furthermore, different (18)F-labelled tissue specific agents are indicated for the detection and monitoring of various malignancies: melanoma, brain tumours, breast cancer, prostate cancer and colorectal cancer. (18)F-fluorodeoxyglucose has been excluded from this summary.

Experiments on a new phosphine-peptide chelator for labelling of peptides with Tc-99m.

A phosphine-containing ligand providing a N-[N-[3-(diphenylphosphino)propionyl]glycyl]-L-S-benzyl-cystein (PNNS) donor atomset for the chelation of 99mTc was studied in labelling experiments with a model peptide (tetragastrin, cholecystokinin-fragment). The peptide was conjugated to the ligand chelator by active ester chemistry either before or after radiolabelling. Both the chelator-conjugate and the preformed chelate approaches resulted in the same radiolabelled isomers of the ligand peptide. Sequence and reaction conditions influence yield and purity.

[Ketoprofen in the prevention of postoperative pain in abdominal surgery. A multicenter study]. / Il ketoprofene nella profilassi del dolore postoperatorio in chirurgia addominale. Studio multicentrico.

Two-hundred-forty-eight patients undergoing abdominal surgery were admitted to a multicentric clinical trial. The patients were randomly assigned to a single i.v. dose of ketoprofen or acetylsalicylic acid, 15 minutes after the end of operation. Ketoprofen showed a better analgesic activity with a statistically significant difference at 2 and 4 hours after administration. Two patients treated with ketoprofen reported vomiting and skin rash respectively. The results of this study confirm the efficacy of ketoprofen for the prophylaxis of postoperative pain in abdominal surgery.

Determination of 99Tc in urine by liquid scintillation counting to evaluate internal contamination.

A practical method is described which allows the radiochemical determination of 99Tc in urine. The radionuclide is recovered as tetraphenylarsonium pertechnetate by coprecipitation with tetraphenylarsonium perchlorate and its activity is counted by the liquid scintillation technique. The lower limit of detection, assumed equal to three standard deviations of the blank activity, is about 2 pCi in 50 ml of urine and permits an evaluation of an internal contamination of one investigation level even four months after intake. The urinary excretion function of 99Tc is calculated from experimental data reported in the literature for 99mTc and is used to establish derived investigation levels on the basis of annual limits on intake recommended by the International Commission on Radiological Protection. The illustrated method is sensitive enough to perform accurate evaluations every three months, a frequency suitable for radiological protection of workers.

[Acute pancreatitis associated with a calculosis of the gallbladder in childhood. Review of the literature and personal experience]. / Pancreatite acuta associata a calcolosi della colecisti in età pediatrica. Revisione della letteratura e nostra esperienza.

The authors present a case of a thirteen year old girl with acute hemorrhagic pancreatis and cholelithiasis. They show the rarity of this pathology in children underlaying the difficulty of an early diagnosis emphasizing the lack of specific symptoms with the exception of an increase of amylase in the saliva and in the serum, the only laboratory data. Moreover, they underlay a more favourable prognosis in children than in adults.