Licia Uccelli

Performance evaluation of the fully engineered YAP-(S)PET scanner for small animal imaging

At the Department of Physics of the University of Pisa, a new and fully engineered version of the YAP-(S)PET small animal scanner has been recently installed. The new YAP-(S)PET is able to perform both PET and SPECT studies on small animals. The scanner is made up of four heads: each one is composed of a 4times4 cm2 YAlO3:Ce (or YAP:Ce) matrix of 20times20 elements, 2times2times25 mm3 each, coupled to a PS-PMT (Hamamatsu R2486). The four modules are positioned on a rotating gantry. The switching to the SPECT modality is easily made by mounting a high resolution parallel hole (0.6 mm Phi, 0.15 mm septum) lead collimator in front of each crystal. This paper reports the performance of the system in terms] of absolute sensitivity and spatial resolution for both PET and SPECT modalities. The scatter fraction and noise-equivalent count rate (NEC) for a mouse phantom for different energy windows have been measured. Images of phantoms and animals are also presented

A class of asymmetrical nitrido 99mTc heterocomplexes as heart imaging agents with improved biological properties.

Asymmetrical heterocomplexes containing a terminal technetium-nitrogen multiple bond coordinated to one diphosphine ligand (PNP) and one dithiocarbamate ligand (DBODC), were obtained through a simple two-step procedure under controlled conditions. The resulting complexes [99mTc(N)(PNP)(DBODC)]+ are monocationic, and possess a distorted square-pyramidal geometry where the Tc≡N multiple bond occupies an apical position and the diphosphine and dithiocarbamate ligands span the residual four coordination positions on the basal plane through the two phosphorus atoms and the two sulfur atoms, respectively. Biodistribution data in rats demonstrated that these complexes were rapidly extracted by the myocardium, and retained in this region for a prolonged time. After a few minutes post-injection, lung uptake became negligible, and liver washout was extremely rapid and quantitative. Analysis of heart/liver uptake ratios for these complexes revealed that their values increased exponentially in time, and after 60 min post-injection liver activity was almost completely eliminated into the intestine. Comparison with heart/liver ratios determined for 99mTc sestamibi and 99mTc tetrfosmin showed that values for these latter compounds were approximately 10 times lower than those measured for [99mTc(N)(PNP)(DBODC)]+ complexes at 60 min post-injection. In conclusion, the monocationic tracers [99mTc(N)(PNP)(DBODC)]+ exhibit high myocardial uptake in rats and dramatically high heart/lung and heart/liver ratios, suggesting that this novel class of perfusion agents could be conveniently employed to obtain heart images with superior imaging quality.

High-yield synthesis of the terminal 188Re≡N multiple bond from generator-produced [188ReO4]−

Abstract A novel procedure for the high-yield preparation of Re-188 radiopharmaceuticals containing a terminal Re≡N multiple bond is described. This method involves the reaction of [ 188 Re][ReO 4 ] − with N -methyl S -methyl dithiocarbazate (DTCZ), as donor of nitrido nitrogen atoms, sodium oxalate and SnCl 2 to afford a mixture of two intermediate compounds. When this mixture is reacted with the sodium salt of a dithiocarbamate ligand (L) of the type Na[R 2 N-C(=S)S] (R = CH 3 , CH 3 CH 2 , CH 3 CH 2 CH 2 ), the formation of the bis-substituted, neutral complexes [ 188 Re][Re(N)(L) 2 ] is easily obtained in high yield (> 95%). The complexes [ 188 Re][Re(N)(L) 2 ] were characterized by chromatographic methods, and by comparison with the corresponding complexes prepared at macroscopic level starting from a non-radioactive rhenium precursor. Biodistribution studies were carried out in rats. Results showed that the complexes [ 188 Re][Re(N)(L) 2 ] exhibited the same biological behavior of the analogous Tc-99m complexes reported previously. The easy application of the new synthetic procedure indicates that it could be conveniently employed for preparing a large class of new Re-188 complexes having potential utilization in nuclear medicine as therapeutic agents.

Brain perfusion SPET and proton magnetic resonance spectroscopy in the evaluation of two systemic lupus erythematosus patients with mild neuropsychiatric manifestations

The diagnosis of central nervous system (CNS) involvement appears to be a major problem in systemic lupus erythematosus (SLE), especially when the clinical signs are non-specific or neuroimaging is unremarkable. Two SLE patients with mild neuropsychiatric manifestations were studied with magnetic resonance imaging (MRI), single photon emission tomography (SPET) and localized proton magnetic resonance spectroscopy (H-1 MRS). MRI was normal in both patients. SPET revealed areas of hypoperfusion in both patients. H-1 MRS demonstrated metabolic abnormalities in the regions corresponding to the hypoperfused areas. A correlation between H-1 MRS and SPET was noted: patients with mild neuropsychiatric SLE may have disturbances evident on SPET and H-1 MRS in the presence of normal anatomy on MRI, suggesting that CNS involvement in SLE has very strong physiological and neurometabolic components in individual patients.

Technetium-99m sestamibi leg scintigraphy for non-invasive assessment of propionyl-l-carnitine induced changes in skeletal muscle metabolism

Carnitine derivatives, such as propionyl-l-carnitine (PLC), have been shown to improve walking distance in patients with obstructive peripheral artery disease (PAOD). The aim of this study was to ascertain whether technetium-99m sestamibi leg scintigraphy may be a useful tool in the evaluation of changes in skeletal muscle metabolism induced by chronic therapy with PLC. Twenty patients with clinical and instrumental evidence of PAOD were randomly assigned to a 3-month period of therapy with either PLC or placebo. Rest99mTc-sestamibi leg scintigraphy and echo-Doppler sonography were performed on all subjects immediately before and upon completion of the treatment period. At the end of the protocol the following results were observed in patients who underwent PLC administration: (a) a significant increase in both thigh and calf99mTc-sestamibi uptake, in comparison with baseline values (P<0.001); (b) the absence of statistically significant modifications of Doppler blood flow indices of the lower limbs. In conclusion, after chronic administration of PLC, a significant increment in skeletal muscle uptake of99mTc-sestamibi was demonstrated without any apparent change in regional blood flow. This fact, if proven in further studies, may suggest a role for this tracer as a non-invasive probe of tissue bioenergetics.

Expression of ras oncogene p21 protein in normal and neoplastic ovarian tissues : correlation with histopathologic features and receptors for estrogen, progesterone, and epidermal growth factor

OBJECTIVE The aim of the study was to investigate the biologic significance of p21 expression in normal and neoplastic ovarian tissues. STUDY DESIGN Western blotting analysis of p21/ras oncoprotein was conducted in a group of 14 normal and cystic ovaries, six benign tumors, 42 primary ovarian cancers, and 15 omental metastases. RESULTS Levels of p21 were similar in normal and cystic ovaries and in benign tumors, whereas they were significantly higher in malignant tumors than in control tissues (median 1.91, range 0.12 to 5.00 vs median 1.03, range 0.32 to 2.20; p = 0.023) and in omental metastases than in primary ovarian carcinomas (median 3.05, range 0.55 to 5.72 vs median 1.97, range 0.12 to 5.00; p = 0.14). We found no correlation between p21 expression and histopathologic or clinical characteristics. Estrogen receptor-positive and progesterone receptor-positive tumors expressed higher p21 levels than did estrogen receptor-negative and progesterone receptor-negative tumors (p < 0.05), but no correlation with epidermal growth factor receptor status was found. In the univariate analysis of survival p21 positivity showed a negative prognostic value. CONCLUSION The enhancement of p21 protein is associated in the ovarian tissue with the malignant phenotype and the acquisition of metastatic potential.

Whole-Body Biodistribution and Radiation Dosimetry of the New Cardiac Tracer 99mTc-N-DBODC

Our purpose was to evaluate the safety profile and biodistribution behavior in healthy human volunteers of the new myocardial perfusion tracer bis[(dimethoxypropylphosphanyl)ethyl]ethoxyethylamine N,N′-bis(ethoxyethyl)dithiocarbamato nitrido technetium(V) (99mTc-N-DBODC). Methods: Ten healthy male volunteers were injected with 99mTc-N-DBODC under both stress and rest conditions. Anterior and posterior planar γ-camera images were collected at 5, 30, 60, 240, and 1,440 min after injection, with organ uptake quantified by region-of-interest analysis. Tracer kinetics in body fluids were determined by collecting blood and urine samples at different time points. Results: After injection, 99mTc-N-DBODC showed significant accumulation in the myocardium and prolonged retention. Under rest conditions, uptake in the heart, lungs, and liver at 5 min after injection was 1.67% ± 0.13%, 1.16% ± 0.07%, and 10.85% ± 1.72%, respectively, of administered activity. Under stress conditions, heart uptake was significantly higher (2.07% ± 0.22%). Radioactivity in the liver decreased to 3.64% ± 0.98% and 2.37% ± 0.48% at 60 and 240 min, respectively, after injection. This rapid liver clearance led to favorable heart-to-liver ratios, reaching values of 0.74 ± 0.13 at rest and 1.26 ± 0.28 during exercise 60 min after tracer administration. Radiation dose estimates were comparable to those obtained with other myocardial perfusion cationic compounds. Conclusion: The high uptake in the myocardium and the fast liver washout of 99mTc-N-DBODC will allow SPECT images of the left ventricle to be acquired early and with excellent quality.

Oxo-rhenium(V) mixed-ligand complexes with bidentate functionalized phosphines and tridentate Schiff base ligands

Abstract A series of monooxo-rhenium(V) mixed-ligand complexes containing bidentate functionalized phosphines and tridentate Schiff base (SB) ligands have been synthesized via ligand-exchange reactions starting from labile Re(V) precursors. A convenient route of synthesis is provided by the isolation of intermediate species such as [Re(O)(Ln)Cl3]− (1–3), (Ln=bidentate phosphino-phenolato or phosphino-carboxylato ligands). Subsequent addition of the relevant SB affords neutral mixed-ligand complexes of general formula [Re(O)(Ln)(SBm)] (1–3m). By reversing the addition of the two ligands, i.e. SB first followed by functionalized phosphine, the resulting mixed-ligand species do not change formulation. Conventional spectroscopic techniques and the single-crystal X-ray structure determination of the two representative compounds ([Re(O)(L1)(SBa)] (1a) and [Re(O)(L1)(SBb)] (1b)) reveal a distorted octahedral geometry around the rhenium center, with the phosphino-phenolato oxygen located trans to the oxo group and the equatorial sites filled by the SB donors and the phosphine phosphorus. It is worth noting that technetium chemistry works quite differently under the same reaction conditions. In fact, no intermediate species of the type [Tc(O)(Ln)Cl3]− can be isolated with [Tc(O)Cl(L1)2] and reduced [Tc(Ln)3] being the major compounds.

Labeling of fatty acid ligands with the strong electrophilic metal fragment [99mTc(N)(PNP)]2+ (PNP=diphosphane ligand).

The electrophilic metal fragment [(99m)Tc(N)(PNP)](2+) (PNP=diphosphane ligand) has been employed for the labeling of fatty acid chains of different lengths. To provide a site-specific group for the attachment of the metallic moiety, the fatty acid derivatives were functionalized by appending a bis-mercapto or, alternatively, a dithiocarbamato pi-donor chelating systems to one terminus of the carbon chain to yield both dianionic and monoanionic bifunctional ligands (L). The resulting complexes, [(99m)Tc(N)(PNP)(L)] (0/+), exhibited the usual asymmetrical structure in which a Tc(triple bond)N group was surrounded by two different bidentate chelating ligands. Dianionic ligands gave rise to neutral complexes, while monoanionic ligands afforded monocationic species. Biodistribution studies were carried out in rats. An isolated perfused rat heart model was employed to assess how structural changes in the radiolabeled fatty acid compound affect the myocardial first pass extraction. Results showed that only monocationic complexes accumulated in myocardium to a significant extent. Conversely, neutral complexes were not efficiently retained into the heart region and rapidly washed out. In isolated perfused rat heart experiments, monocationic complexes exhibited a behavior similar to that of the monocationic flow tracers (99m)Tc-MIBI and (99m)Tc-DBODC with almost identical extraction values, a result that could be attributed to the presence of the monopositive charge. Instead, a slightly lower myocardial extraction was found for neutral complexes. Comparison of the observed kinetic behavior of neutral complexes in the isolated perfused rat heart model with that of the myocardial metabolic tracer [(123)I]IPPA revealed that the introduction of the metallic moiety partially hampers recognition of the labeled fatty acids by cardiac enzymes, and consequently, their behavior did not completely reflect myocardial metabolism.

Biodistribution of nanostructured lipid carriers: A tomographic study

This study describes the preparation, characterization, and biodistribution of radiolabelled nanostructured lipid carriers (NLCs) especially designed for in vivo tomographic study. A preliminary formulative study was conducted in order to incorporate (99m)Tc based tracer in NLCs. At this aim a (99m)Tc complex containing a terminal (99m)Tc ≡ N multiple bond ([(99m)Tc]N-DBODC2) has been synthesized and included in NLCs produced by a stirring and ultrasonication method. The morphological and dimensional characteristics of the produced NLCs have been accurately investigated by a number of specific techniques, including: cryogenic transmission electron microscopy, X-ray, photon correlation spectroscopy and sedimentation field flow fractionation. The obtained NLCs were employed for achieving in vivo tomographic images of the rat body by small-animal SPECT scanner that enabled the investigation of NLC biodistribution after intraperitoneal, intravenous, intranasal and oral administration. NLC production protocol allowed to firmly encapsulate the radiotracer within the nanoparticles. In vivo studies evidenced that NLC remained stable in vivo, suggesting their suitability as controlled release system for drugs and radiochemical for therapeutic and diagnostic purposes. Moreover the high resolution images obtained by the SPECT technique allowed to detect NLC presence in brown fat tissue, suggesting NLC therapeutic application for treating human obesity and related metabolic disorders.