Complexation of trivalent lanthanides by three diphosphonate ligands in the blood plasma

It has been shown that ¹⁵³Sm complexed with the bone seeking ligand ethylene-diaminetetramethylene phosphonate (EDTMP) is effective in pain palliation therapy of bone cancer. Blood plasma models for this ligand with Sm(III) and Ho(III) have been successfully constructed explaining the differences between ¹⁵³SmEDTMP and ¹⁶⁶HoEDTMP. The latter isotope is preferred because of its more energetic β particle, thought to improve the therapeutic effect of the radiopharmaceutical. However, ¹⁶⁶HoEDTMP is not an effective pain palliation agent and consequently the search for a more effective bone cancer therapeutic radiopharmaceutical involving ¹⁶⁶Ho continues. A ligand is being sought which complexes Ho(III) with a formation constant high enough to survive competition from blood plasma ligands but not so high to prevent ¹⁶⁶Ho from being accessible to metastases. EDTMP is unsuitable as such a ligand because of its inability to compete with citrate for complexation of Ho(III). For this study three diphosphonate ligands applied in radiation imaging of bone or nonradiative treatment of osteoporosis were chosen. They are APD (1-hydroxy-3-aminopropylidene- diphosphonic acid), MDP (methylenediphosphonic acid) and HEDP (1- hydroxy-ethylene-diphosphonic acid). Formation constants for the complexation of Ca(II), Mg(II), Zn(II), Sm(III) and Ho(III) with all of these ligands were measured using potentiometry and polarography. The latter was used to complement potentiometry in systems where precipitates formed. The complexation of Cd(II) by HEDP was used to compare the two techniques and to show that the values found by either technique are comparable. NMR studies were attempted on some complexes in solution to investigate the role the of the hydroxy-group (APD and HEDP) in complexation. The program ECCLES was used together with the formation constants measured in this study to predict the speciation of Ho(III) and Sm(III) with these three ligands in blood plasma. The results gathered for Ho(III) and APD were used as an indication and in an application to an ethical committee before animal testing. A baboon test was carried out using ¹⁶⁶HoAPD, the most promising system. The resulting bone-uptake and side-effects found in the animal study confirmed the predictions made by ECCLES. It proved that ¹⁶⁶HoAPD would be ineffective as a therapeutic agent due to high liver uptake. Valuable information on how a future radiopharmaceutical should be designed was obtained in this study

Tetra­ethyl­ammonium tricarbonyl­chlorido­(pyrazine-2-carboxyl­ato-N 1,O)rhenate(I)

In the title complex, (C8H20N)[Re(C5H3N2O2)Cl(CO)3], the ReI atom is coordinated facially by three carbonyl groups; the bidentate pyrazine­carboxyl­ato ligand and a chlorine atom complete the distorted octa­hedral coordination

Kinetic study of uranium residue dissolution in ammonium carbonate media

The purpose of this study was to determine the kinetics of the dissolution of a uranium residue in ammonium carbonate media. The residue is generated in the production of medical isotopes. The effects of parameters, such as varying peroxide and carbonate concentrations, dissolution time as well as temperature on the extraction rate have been separately studied. Results indicate complete dissolution of the residue at 60 oC, after thirty minutes, in ammonium carbonate solution enriched with hydrogen peroxide. The yield and rate of uranium extraction were found to increase as a function of both temperature, in the range of 25-60 oC, and hydrogen peroxide concentration. The extraction process was governed by chemical reaction as the activation energy was found to be 45.5 kJ/mol. The order of reaction with respect to uranium concentration was found to be approximately first order.Necsa, the Department of Materials Science and Metallurgical Engineering (University of Pretoria) and the Department of Trade and Industries.http://link.springer.com/journal/10967hb201

Article towards facile radiolabeling and preparation of gallium-68-/bismuth-213-dota-[thi8, met(O2)11]-substance p for future clinical application : first experiences

Please read abstract in the article.The Nuclear Technologies in Medicine and the Biosciences Initiative (NTeMBI) and the Technology Innovation Agency (TIA).http://www.mdpi.com/journal/pharmaceuticspm2022Nuclear Medicin

Tetra­ethyl­ammonium tricarbonyl­chlorido(quinoxaline-2-carboxyl­ato-κ2 N 1,O)rhenate(I)

In the title compound, (C8H20N)[Re(C9H5N2O2)Cl(CO)3], the ReI atom is coordinated facially by three carbonyl groups, the bidentate quinoxaline-2-carbaldehyde ligand and a chloride atom, forming a distorted octahedral geometry.. The crystal packing is controlled by C—H⋯O hydrogen bonding and π–π stacking inter­actions involving the benzene rings, with a centroid–centroid distance of 3.4220 (1) Å

Antibiotic-derived radiotracers for positron emission tomography : nuclear or “unclear” infection imaging?

The excellent features of non-invasive molecular imaging, its progressive technology (real-time, whole-body imaging and quantification), and global impact by a growing infrastructure for positron emission tomography (PET) scanners are encouraging prospects to investigate new concepts, which could transform clinical care of complex infectious diseases. Researchers are aiming towards the extension beyond the routinely available radiopharmaceuticals and are looking for more effective tools that interact directly with causative pathogens. We reviewed and critically evaluated (challenges or pitfalls) antibiotic-derived PET radiopharmaceutical development efforts aimed at infection imaging. We considered both radiotracer development for infection imaging and radio-antibiotic PET imaging supplementing other tools for pharmacologic drug characterization; overall, a total of 20 original PET radiotracers derived from eleven approved antibiotics.The Nuclear Medicine Research Infrastructure NPC.http://www.angewandte.orgam2023Nuclear Medicin

Fluorine-18-Fluoroethylcholine PET/CT in the detection of prostate cancer : a South African experience

OBJECTIVE : Imaging with fluorine-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) has, until recently provided disappointing results with low sensitivity ranging from 31%-64% in patients with well-differentiated prostate cancer (PC) at all prostatic specific antigen (PSA) levels while fluorine-18-fluoroethylcholine (18F-FECh) PET/CT showed about 85% sensitivity in restaging patients after relapse. We present our experience of the sensitivity of 18F-FECh PET/CT in the early stages of PC. SUBJECT AND METHODS : Fifty patients were prospectively recruited and imaged, of which 40 fulfilled all inclusion criteria. Our patients had an average age of 65.5 years. Fifteen patients were referred for initial staging, with the remaining 25 referred for restaging and all patients had histologically confirmed adenocarcinoma. Patients were imaged by 18F-FECh PET/CT. Findings were evaluated qualitatively and quantitatively and compared to the results of histology, PSA, Gleason score and bone scintigraphy. The prostate SUV max was also used. RESULTS : Thirty-one patients demonstrated abnormal pelvic- and or extrapelvic findings on 18F-FECh PET/CT, which was consistent with malignant or metastatic involvement. The prostate SUVmax could not be used to predict the presence or absence of metastatic disease. CONCLUSION : Findings of this paper suggest that 18F-FECh PET/CT in 30/40 cases (estimated as 75%) was helpful in the initial staging, restaging and lymph node detection of patients with PC. The SUVmax was not helpful. We diagnosed more PC cases in our African-American patients as compared to the Caucasian patients.http://nuclmed.web.auth.gr/hb2016Nuclear MedicineUrolog

Single photon emission tomography in the diagnostic assessment of cardiac and vascular infectious diseases

Please read abstract in the articlehttp://www.benthamscience.comcrp/index.htmhj2022Nuclear Medicin

Combination of terbium-161 with somatostatin receptor antagonists—a potential paradigm shift for the treatment of neuroendocrine neoplasms

Purpose: The β¯-emitting terbium-161 also emits conversion and Auger electrons, which are believed to be effective in killing single cancer cells. Terbium-161 was applied with somatostatin receptor (SSTR) agonists that localize in the cytoplasm (DOTATOC) and cellular nucleus (DOTATOC-NLS) or with a SSTR antagonist that localizes at the cell membrane (DOTA-LM3). The aim was to identify the most favorable peptide/terbium-161 combination for the treatment of neuroendocrine neoplasms (NENs). Methods: The capability of the 161Tb- and 177Lu-labeled somatostatin (SST) analogues to reduce viability and survival of SSTR-positive AR42J tumor cells was investigated in vitro. The radiopeptides' tissue distribution profiles were assessed in tumor-bearing mice. The efficacy of terbium-161 compared to lutetium-177 was investigated in therapy studies in mice using DOTATOC or DOTA-LM3, respectively. Results: In vitro, [161Tb]Tb-DOTA-LM3 was 102-fold more potent than [177Lu]Lu-DOTA-LM3; however, 161Tb-labeled DOTATOC and DOTATOC-NLS were only 4- to fivefold more effective inhibiting tumor cell viability than their 177Lu-labeled counterparts. This result was confirmed in vivo and demonstrated that [161Tb]Tb-DOTA-LM3 was significantly more effective in delaying tumor growth than [177Lu]Lu-DOTA-LM3, thereby, prolonging survival of the mice. A therapeutic advantage of terbium-161 over lutetium-177 was also manifest when applied with DOTATOC. Since the nuclear localizing sequence (NLS) compromised the in vivo tissue distribution of DOTATOC-NLS, it was not used for therapy. Conclusion: The use of membrane-localizing DOTA-LM3 was beneficial and profited from the short-ranged electrons emitted by terbium-161. Based on these preclinical data, [161Tb]Tb-DOTA-LM3 may outperform the clinically employed [177Lu]Lu-DOTATOC for the treatment of patients with NENs

Preclinical evaluation of 68Ga-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-ubiquicidin as a radioligand for PET infection imaging

Antimicrobial peptides such as ubiquicidin (UBI) are believed to differentiate between mammalian and bacterial or fungal cells. (99m)Tc-UBI29-41 was previously tested for detecting infection in humans using SPECT. For the present study, the UBI fragment UBI29-41 (TGRAKRRMQYNRR) was conjugated to 1,4,7-triazacyclononane-triacetic acid (NOTA), radiolabeled with (68)Ga, and investigated in a rabbit infection model. METHODS : (68)Ga was obtained from a 1.85-GBq (68)Ge/(68)Ga generator. New Zealand White rabbits were anesthetized with ketamine/medetomidine before tracer administration and placed in a clinical PET/CT scanner. (68)Ga-1,4,7-triazacyclononane-1,4,7-triacetic-acid-ubiquicidin29-41 ((68)Ga-NOTA-UBI29-41) was formulated in saline solution, and 101 ± 41 MBq were administered intravenously. The tracer distribution was studied by PET/CT imaging in animals (a) that were healthy, (b) bearing muscular Staphylococcus aureus infections and turpentine oil-induced muscular inflammations, and (c) bearing ovalbumin-induced lung inflammations. Static PET/CT imaging was performed at different time intervals up to 120 min after injection. For calculation of target-to-nontarget ratios, standardized uptake values were normalized against healthy thigh muscle, representing nontargeted tissue. RESULTS : PET/CT images of healthy animals showed predominant distribution in the kidneys, liver, and bladder; heart and spleen showed moderate, declining uptake, only. The biologic half-life in blood was 29 min. Urinary accumulation of (68)Ga-NOTA-UBI29-41 peaked at 3.8 ± 0.91 percentage injected dose per gram (%ID) at 120 min, and 88 ± 5.2 %ID was recovered in total urine. (68)Ga-NOTA-UBI29-41 imaging in (b) selectively visualized the muscular infection site and was differentiated from sterile inflammatory processes. Standardized uptake value ratios for muscles (infected/inflamed) were 2.9 ± 0.93, 2.9 ± 0.50, 3.5 ± 0.86, and 3.8 ± 0.90 at 5, 30, 60, and 90 min after injection, respectively. Rabbit lungs with asthma showed insignificant uptake. CONCLUSION : (68)Ga-NOTA-UBI29-41 was strongly localized in bacteria-infected areas and minimally detected in a sterile inflammation area in rabbit muscles. The findings propose this compound to be an excellent first-line PET/CT tracer to allow the distinguishing of infection from inflammation.http://jnm.snmjournals.org/hb201