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A new radio-HPLC detection system for measuring radioactivity in plasma samples during Positron Emission Tomography [PET] studies was developed. It is based on detecting both the positron and one of the annihilation photons. The system focused on improving the measurement of radioactivity concentrations on an unmetabolized positron emitting a radiopharmaceutical [PER] in the presence of its radioactive metabolites, all containing the same positron emitter. This paper presents a new detection configuration that improves the minimal detectible activity (MDA), simplify the measuring systems and reduces the error caused by the metabolites. The detector is based on a plastic scintillator and a BGO scintillation crystal, that produces different light output spectra for signal and noise events. By summing the positron and the annihilated photon light outputs, different spectra are obtained for the metabolite and for the parent compound tracer and for tracer marked by different positron emitting isotopes. This new detection system can improve quantitative analysis of plasma samples. The spectrum change provides up to a three-fold improvement in sensitivity compared to the currently used detection systems that measure only the annihilation coincidence events. Results showed that for 11 C the MDA was improved by approximately 520%. Furthermore, it provides the additional advantage of reliability by providing a method for separating the signal and noise readings from the gross detector readout. Accurate reconstruction algorithm of the signal was achieved over a wide measuring range even when the signal was only 5% of the gross measurement., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Challenges facing cardiovascular imaging necessitate innovation of better radiopharmaceuticals to augment or replace the existing ones. This research assesses the ability and competency of radioiodinated esmolol as a potential cardio selective imaging agent. Radioiodinated esmolol was synthesized with 97.3 ± 0.3% radiochemical yield and with high stability up to 48 h at room temperature as well as in rat serum. Molecular modeling study was performed to confirm the binding of iodinated esmolol to β 1 -adrenergic receptor. Its biodistribution studies in normal Swiss albino mice showed high heart uptake (38.5 ± 0.11%ID/g at 5 min p.i.), heart/liver ratio nearly 3.85:1 and heart/lungs ratio was about 7:1 at 5 min p.i. The evidenced selectivity of the radioiodinated esmolol to β 1 -adrenoceptor was confirmed by prior injection of cold esmolol. Gamma camera biodistribution pattern showed that radioiodinated esmolol accumulated selectively in heart., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In this study, we describe the radiosynthesis of [ 18 F]AV1451 in terms of its pharmaceutical quality and characterise its physical and biological properties. We performed an in vitro serum stability study in fresh human plasma and a plasma protein binding study. The radiochemical yield was 24% (decay corrected), and the product met all regulatory quality requirements. We found that this compound is stable in fresh human plasma and binds tightly to plasma proteins, especially lipoproteins., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

This paper describes the evaluation of [(R)-2-Amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-pentaacetic acid (CHX-A''-DTPA-NCS) and 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA-NCS) as bifunctional chelators for 177 Lu. While 177 Lu-CHX-A''-DTPA-NCS could be obtained in high yields at equimolar ratios of lutetium to CHX-A''-DTPA-NCS, >95% yield of 177 Lu-NOTA-NCS could be achieved at 1:2M ratio of lutetium to NOTA-NCS. Trace metals reduced the yields of 177 Lu-NOTA-NCS significantly as compared to 177 Lu-CHX-A''-DTPA-NCS. In vitro stability of 177 Lu-CHX-A''-DTPA-NCS was also superior to 177 Lu-NOTA-NCS. It could be concluded from this study that among the two chelators evaluated, CHX-A''-DTPA-NCS is more appropriate for preparation of 177 Lu radiopharmaceuticals., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The cartilage-targeting strategy is based on the strong affinity of quaternary ammonium (QA) functions for cartilage proteoglycans. We use a bifunctional agent containing QA moiety and a polyazamacrocycle structure able to complex technetium-99m. (99m)Tc-NTP 15-5 was selected for its high stability and its high affinity for proteoglycans in vivo. Labeling conditions of NTP 15-5 were optimized, and a lyophilized kit was developed for radiolabeling of (99m)Tc-NTP 15-5 (radiochemical yields 94.6±1.8%). (99m)Tc-NTP 15-5 was stable and resulted in favorable biological evaluations., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Tamoxifen [TAM ([Z]-2-[4-(1,2-diphenyl-1-di-butenyl)-phenoxy]-N,N-dimethylethanamine)] has been used as an antiestrogen drug for treatment and prevention of human breast cancer. Tamoxifen was labeled with 131I using iodogen as an oxidizing agent. Mass spectroscopy of the cold standard showed that the labeling occurs in ortho position to the phenyl ether position of TAM as expected. Quality control, radiochemical yield and stability were established using the radioelectrophoresis method. The radiolabeled compound maintained its stability throughout working period of 24 h. Scintigraphic imaging was performed and tissue distribution was determined in Albino Wistar rats. According to biodistribution and imaging experiments the radiolabeled compound presented estrogen receptor (ER) specificity and it was uptaken by endometrium as well as breast tissue.

99mTc-UBI 29-41 is an antimicrobial peptide fragment that directly radiolabeled with 99mTc shows high in vitro and in vivo stability, rapid background clearance, minimal accumulation in non-target tissues and rapid detection of infection sites. Molecular mechanics (MM) calculation has been an essential tool in explaining experimental results associated with molecular recognition and stability. This work is an attempt to explain the 99mTc-UBI 29-41 specificity for bacteria and to understand from a structural point of view, the experimental results indicative of a molecular recognition and stability not well favored for two other cationic peptides (99mTc-Tat-1-Scr and 99mTc-Tat-2-Scr ) used as control. Structures of 99mTc-UBI, 99mTc-Tat-1-Scr, 99mTc-Tat-2-Scr and of the corresponding free cationic peptides were built and the optimized structures, in the best stable configurations, were calculated by a MM procedure. In order to correlate the calculated and experimental results, in vitro stability tests with cysteine challenge and stability to dilution in human serum and in saline solution, were performed for the three labeled cationic peptides. The three complexes can be represented by the general formula [Tc(V)(O)(H2O)2(Lysn=1,2-Argn=0,1-peptide)]10+,11+. The potential energies were 104.5, 95.6 and 90.8 kcal/mol for 99mTc-Tat-1-Scr, 99mTc-Tat-2-Scr and 99mTc-UBI 29-41, respectively. Experimental and calculated results were in good agreement. It is thus possible to predict and explain that in similar solution media 99mTc-Tat-2-Scr would be more stable than 99mTc-Tat-1-Scr and why 99mTc-UBI shows the highest stability. In conclusion, the in vitro specific binding to bacteria and the accumulation at infection sites in humans of 99mTc-labeled UBI could be the result of its high thermodynamic stability, selectivity and stereospecificity.

The peripheral-type benzodiazepine receptors (PBRs) are only minimally expressed in normal brain parenchyma, where they are primarily localized in glial cells. Their basal expression rises in different neurodegenerative disorders, due to the presence of infiltrating inflammatory cells and activated microglia. [11C]PK11195, a selective PBR antagonist, has been used for the in vivo PET monitoring of neurodegeneration in clinical observations. We recently developed and labeled with carbon-11 three new carboxamide derivatives: [11C]VC193M, [11C]VC195 and [11C]VC198M. Aim of this study was to evaluate these ligands for the in vivo measuring of PBRs expression in neurodegenerations and compare their kinetic behavior with that of the reference tracer [11C]PK11195. Radioligands were evaluated in a preclinical model of Huntington's disease consisting in the monolateral striatal injection of quinolinic acid (QA). Activated microglia and astrocytic gliosis was present only within the affected striatum. A concomitant increase in radioactivity accumulation was observed for all the tracers examined (P<0.01). Among the new compounds, [11C]VC195 showed higher levels of lesioned/unlesioned striatum ratios (3.28+/-0.44), in comparison with [11C]VC193M and [11C]VC198M (2.69+/-0.53 and 1.52+/-0.36, respectively), but slightly inferior to that observed for [11C]PK11195 (3.76+/-1.41).In conclusion, the results of the study indicate that [11C]VC195 is a promising candidate for in vivo PET monitoring of neurodegenerative processes but its in vivo behavior overlap that of [11C]PK11195.

A new isonitrile ligand 3,3,5-trimethyl cyclohexylisonitrile (TMCHI) and its copper salt [Cu(TMCHI)4BF4] were synthesized and characterized by IR and elemental analysis. 99mTc-TMCHI is prepared by direct labeling method with high RCP. In vitro protein binding in albumin, blood retention and biodistribution of 99mTc-TMCHI in mice indicated that it is mainly accumulated and maintained in blood with a high protein binding rate and low washout rate. The target/non-target ratios in mice are excellent and suggest its use as a cardiac blood pool agent.

Two novel [99mTc] [ SNN/S] "3+1" mixed ligand complexes, where L3H2= o-methylthio-glycinanilide (A) or N-(1-methylthio-phenyl)-ethylenediamine (B) and L1H= isopropanethiol, were synthesized using stannous chloride as reductant and glucoheptonate as transfer ligand. The identifications of [99mTc]-A and [99mTc]-B were established by thin layer chromatography. The radiochemical purity of both complexes was over 90%. The initial biodistribution study in mice demonstrated that both complexes can penetrate the intact blood-brain barrier and exhibit retention in mice brain. The brain uptake (%ID/g) values of [99mTc]-A were 1.68, 1.23, 1.24 and of [99mTc]-B were 1.76, 1.08, 0.90 at 2, 30 and 60 min i.v. postinjection, respectively.

Quantification accuracy in positron emission tomography (PET) using non-pure positron emitters, such as 52Fe, may be influenced by gamma radiation emitted in the decay of these isotopes. High-energy positrons, emitted in the decay of the 52Fe-daughter 52mMn, also affect the quantification accuracy. A specific problem of the 52Fe/52mMn decay chain in vivo is that the kinetics of iron and manganese are different, and that PET cannot discriminate between the two nuclides. The effect of the decay properties of 52Fe/52mMn on the performance of PET was investigated using phantoms. Minor degradation in PET performance was found for 52Fe/52mMn compared to the pure low-energy positron emitter 18F. A method is presented to obtain a correction factor for the 52mMn radioactivity in blood. A model for correction of 52mMn-radioactivity in organs, based on existing data on manganese kinetics, is given. The presented corrections are discussed and illustrated in a patient study.

Oxine, tropolonate, and mercaptopyridine-N-oxide (MPO) have been widely used with 111In for platelet labeling. The use of positron emission tomography (PET) radioisotopes for platelet labeling would offer a higher sensitivity and resolution over conventional imaging. The medium half-life PET radioisotope 55Co (t1/2 = 18.2 hours) would enable quantitative uptake and cell kinetic studies with radiolabeled platelets. To identify the optimal complex for radiolabeling of platelets with 55Co, we investigated the platelet uptake of 57Co-oxine, 57Co-tropolonate, and 57Co-MPO in varying different parameters. The platelet uptake of Co-complexes was generally low (5-12%), dependent on time and temperature of incubation and density of platelets but independent of the amount of radioactivity. These findings are not promising for potential PET application.

Unlabelled: We attempted to label leukocytes with stabilized Tc-99m D,L-HMPAO by methylene blue and sodium phosphate buffer (S-HMPAO)., Methods: The results were compared with unstabilized Tc-99m D,L-HMPAO (U-HMPAO). U-HMPAO was obtained by reconstituting a commercial vial of D,L-HMPAO. Stabilization of the kit was performed by the addition of methylene blue. The leukocytes were labeled using a modified published method. The test samples of S-HMPAO and U-HMPAO were prepared immediately, and stood for 0.5, 1, 2, 4, and 6 h, respectively, at room temperature before analysis., Results: In comparison with U-HMPAO: (1) the radiochemical purity of S-HMPAO was higher; (2) the labeling efficiencies of S-HMPAO labeled leukocytes were higher and consistent; (3) the viability of S-HMPAO labeled leukocytes was as high as the viability of U-HMPAO labeled leukocytes at any time; and (4) the percentages of disintegrated from S-HMPAO labeled leukocytes in plasma were lower., Conclusion: S-HMPAO is more stable than U-HMPAO and can provide higher leukocyte labeling efficiency. S-HMPAO, therefore, has the potential to replace U-HMPAO as a leukocyte-labeling agent.

68Ga-labeled platelets could be useful for positron emission tomographic (PET) studies. In order to identify the optimal chelate for radiolabeling of platelets with 68Ga, we investigated the platelet uptake of 67Ga-oxine, -tropolone and -MPO. The platelet uptake of 67Ga-oxine and -tropolone is very low (< 5%). The platelet uptake of 67Ga-MPO, in contrast, increases with platelet density (highest at 10(9) platelets/ml) up to 18%. Our data provide evidence that only 68Ga-MPO could be useful for PET-studies.

In order to trace the loss of N tau-methylhistamine, a principal metabolite of histamine, during extraction and purification from human plasma and urine samples, N tau-[3H]methylhistamine was prepared in two steps from N alpha t-butoxycarbonylhistamine (II). In the first step, compound II was deprotonated with NaH in an aprotic solvent and treated with [3H]methyl iodide. The products, N alpha t-butoxycarbonyl-N tau-[3H]methylhistamine (III) and N alpha t-butoxycarbonyl-N pi-[3H]methylhistamine (IV), were then hydrolysed with iodotrimethylsilane under mild and short reaction conditions. Facile purification with Sep-Pak silica cartridges gave the combined two isomers of N tau-[3H]methylhistamine and N pi-[3H]methylhistamine in 10.7% radiochemical yield with a radiochemical purity of > 94% and a ratio of approximately 2:1. Improvements in the extraction of methylhistamine using chromatography on Sep-Pak silica cartridges led to an overall recovery of 82.5 +/- 0.3% (n = 3) based upon total [3H]methylhistamine from normal human plasma.