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Background: Bisphosphonates have a high adsorption on calcified tissues and are commonly used in the treatment of bone disorder diseases. Conjugates of bisphosphonates with macrocyclic chelators open new possibilities in bone targeted radionuclide imaging and therapy. Subsequent to positron emission tomography (PET) examinations utilizing Ga-labelled analogues, endoradiotheraphy with Lu-labelled macrocyclic bisphosphonates may have a great potential in the treatment of painful skeletal metastases. Methods: Based on the established pharmaceuticals pamidronate and zoledronate two new DOTA-α-OH-bisphosphonates, DOTA and DOTA(MM1.MZ) were successfully synthesized. The ligands were labelled with the positron emitting nuclide Ga and the β emitting nuclide Lu and compared in in vitro studies and in ex vivo biodistribution studies together with small animal PET and single photon emission computed tomography (SPECT) studies against [F]NaF and a known DOTA-α-H-bisphosphonate conjugate (BPAPD) in healthy Wistar rats. Results: The new DOTA-bisphosphonates can be labelled in high yield of 80 to 95 % in 15 min with post-processed Ga and >98 % with Lu. The tracers showed very low uptake in soft tissue, a fast renal clearance and a high accumulation on bone. The best compound was [Ga]DOTA (SUV = 5.4 ± 0.6) followed by [F]NaF (SUV = 4.8 ± 0.2), [Ga]DOTA (SUV = 4.5 ± 0.2) and [Ga]BPAPD (SUV = 3.2 ± 0.3). [Lu]DOTA showed a similar distribution as the diagnostic Ga complex. Conclusion: The Ga labelled compounds showed a promising pharmacokinetics, with similar uptake profile and distribution kinetics. Bone accumulation was highest for [Ga]DOTA, which makes this compound probably an interesting bone targeting agent for a therapeutic approach with Lu. The therapeutic compound [Lu]DOTA showed a high target-to-background ratio. SPECT experiments showed concordance to the PET scans in healthy rats. [Ga/Lu]DOTA appears to be a potential theranostic combination in the management of disseminated bone metastases. [ABSTRACT FROM AUTHOR]

Fast progressing immuno-PET asks to explore new radionuclides. One of the promising candidates is 90Nb. It has a half-life of 14.6 h that allows visualizing and quantifying biological processes with medium and slow kinetics, such as tumor accumulation of antibodies and antibodies fragments or drug delivery systems and nanoparticles. 90Nb exhibits a positron branching of 53% and an average kinetic energy of emitted positrons of Emean =0.35 MeV. Currently, radionuclide production routes and Nb V labeling techniques are explored to turn this radionuclide into a useful imaging probe. However, efficient separation of 90Nb from irradiated targets remains in challenge. Ion exchange based separation of 90Nb from zirconium targets was investigated in systems AG 1 × 8 - HCl/H2O2 and UTEVA-HCl. 95Nb ( t1/2 = 35.0 d), 95Zr ( t1/2 = 64.0 d) and 92 mNb ( t1/2 = 10.15 d) were chosen for studies on distribution coefficients. Separation after AG 1 × 8 anion exchange yields 99% of 90/95Nb. Subsequent use of a solid-phase extraction step on UTEVA resin further decontaminates 90/95Nb from traces of zirconium with yields 95% of 90/95Nb. A semi-automated separation takes one hour to obtain an overall recovery of 90/95Nb of 90%. The amount of Zr was reduced by factor of 108. The selected separation provides rapid preparation (< 1 h) of high purity 90Nb appropriate for the synthesis of 90Nb-radiopharmaceuticals, relevant for purposes of immuno-PET. Applying the radioniobium obtained, 90/95Nb-labeling of a monoclonal antibody (rituximab) modified with desferrioxamine achieved labeling yields of >90% after 1 h incubation at room temperature. [ABSTRACT FROM AUTHOR]

Recent reports have claimed a superior performance of HEPES buffer in comparison to alternative buffer systems for 67/68 Ga labeling in aqueous media. In this paper we report spectroscopic (1H and 71 Ga NMR), radiochemical, mass spectrometry and theoretical modeling studies on the Ga3+/HEPES system (HEPES = N-2-hydroxyethylpiperazine- N′-2-ethanesulfonic acid) performed with the aim of elucidating a potential contribution of HEPES in the 68/67 Ga radiolabeling process. Our results demonstrate that HEPES acts as a weakly but competitive chelator of Ga3+ and that this interaction depends on the relative Ga3+: HEPES concentration. A by-product formed in the labeling mixture has been identified as a [68 Ga]Ga(HEPES) complex via chromatographic comparison with the nonradioactive analog. The formation of this complex was verified to compete with [68 Ga]Ga(NOTA) complexation at low NOTA concentration. Putative chelation of Ga3+ by the hydroxyl and adjacent ring nitrogen of HEPES is proposed on the basis of 1H NMR shifts induced by Ga3+ and theoretical modeling studies. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Radiolabelling of cocaine-derived 3-phenyltropanes for dopamine transporter positron emission tomography with 18F and 11C is reviewed. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Several studies in the past have shown appreciably higher lung cancer risk estimates associated with smoking exposure among men than among women, while more recent studies in the USA report just the opposite. To evaluate this topic in a European population we conducted a case-control study of lung cancer in three German and three Italian centres. Personal interviews and standardized questionnaires were used to obtain detailed life-long smoking and occupational histories from 3723 male and 900 female cases and 4075 male and 1094 female controls. Lung cancer risk comparing ever-smokers with never-smokers was higher among men (odds ratios (OR) adjusted for age and centre = 16.1, 95% confidence interval (CI) 12.8-20.3) than among women (OR = 4.2, CI 3.5-5.1). Because the smoking habits of women were different from men, we conducted more detailed analyses using comparable levels of smoking exposure. After restriction to smokers and adjustment for other smoking variables, risk estimates did not differ appreciably between genders. The analysis of duration of smoking (0-19, 20-39, 40+ years) adjusted for cigarette consumption and time since quitting smoking revealed similar risk estimates in men (OR = 1.0, 3.3 [CI 2.6-4.2], 4.1 [CI 3.1-5.6]) and women (OR = 1.0, 2.7 [CI 1.7-4.1], 3.3 [CI 1.9-5.8]). The same was true of the analysis of average or cumulative smoking consumption, and also of analyses stratified by different histological types. We conclude that for comparable exposure to tobacco smoke, the risk of lung cancer is comparable in women and men. [ABSTRACT FROM AUTHOR]

An abstract of the article "Toward Robust Estimation of the Components of Forest Population Change" by F. A. Roesch is presented.

Purpose: Periprosthetic loosening is a major complication after total hip and knee arthroplasty. Early and accurate diagnosis is essential to choose the right therapeutic path and to avoid further complications. The aim of the study was to evaluate the diagnostic performance of 68Gallium-Zoledronate ([68Ga]Ga-DOTAZol) PET/CT in detecting periprosthetic loosening in total hip (THA) and total knee arthroplasty (TKA).This retrospective study included 26 patients with painful prosthesis (THA n = 17; TKA n = 16) and clinical suspicion of periprosthetic loosening, but without a confirmed diagnosis. Patients underwent [68Ga]Ga-DOTAZol PET/CT at least one year post-implantation. Diagnosis was confirmed through revision surgery or long-term clinical follow-up, with an observation period of at least 6 months. The analysis included both an assessment of the prosthesis as a unit and a separate evaluation of the individual components. Statistical analysis involved calculating sensitivity, specificity and accuracy using SPSS.Overall, a sensitivity of 77.8%, a specificity of 95.8% and an accuracy of 90.9% were found for detecting periprosthetic loosening, when considering the prosthesis as a unit. Individual component analyses showed a sensitivity of 71.4% and specificity of 96.2%.The use of [68Ga]Ga-DOTAZol PET/CT in periprosthetic loosening is a remarkable diagnostic tool and a promising approach. In comparison to established radionuclide tracers, 68Gallium-Zoledronate offers notable advantages due to its availability via 68Ge/68Ga-generators, improving its potential for clinical application.Methods: Periprosthetic loosening is a major complication after total hip and knee arthroplasty. Early and accurate diagnosis is essential to choose the right therapeutic path and to avoid further complications. The aim of the study was to evaluate the diagnostic performance of 68Gallium-Zoledronate ([68Ga]Ga-DOTAZol) PET/CT in detecting periprosthetic loosening in total hip (THA) and total knee arthroplasty (TKA).This retrospective study included 26 patients with painful prosthesis (THA n = 17; TKA n = 16) and clinical suspicion of periprosthetic loosening, but without a confirmed diagnosis. Patients underwent [68Ga]Ga-DOTAZol PET/CT at least one year post-implantation. Diagnosis was confirmed through revision surgery or long-term clinical follow-up, with an observation period of at least 6 months. The analysis included both an assessment of the prosthesis as a unit and a separate evaluation of the individual components. Statistical analysis involved calculating sensitivity, specificity and accuracy using SPSS.Overall, a sensitivity of 77.8%, a specificity of 95.8% and an accuracy of 90.9% were found for detecting periprosthetic loosening, when considering the prosthesis as a unit. Individual component analyses showed a sensitivity of 71.4% and specificity of 96.2%.The use of [68Ga]Ga-DOTAZol PET/CT in periprosthetic loosening is a remarkable diagnostic tool and a promising approach. In comparison to established radionuclide tracers, 68Gallium-Zoledronate offers notable advantages due to its availability via 68Ge/68Ga-generators, improving its potential for clinical application.Results: Periprosthetic loosening is a major complication after total hip and knee arthroplasty. Early and accurate diagnosis is essential to choose the right therapeutic path and to avoid further complications. The aim of the study was to evaluate the diagnostic performance of 68Gallium-Zoledronate ([68Ga]Ga-DOTAZol) PET/CT in detecting periprosthetic loosening in total hip (THA) and total knee arthroplasty (TKA).This retrospective study included 26 patients with painful prosthesis (THA n = 17; TKA n = 16) and clinical suspicion of periprosthetic loosening, but without a confirmed diagnosis. Patients underwent [68Ga]Ga-DOTAZol PET/CT at least one year post-implantation. Diagnosis was confirmed through revision surgery or long-term clinical follow-up, with an observation period of at least 6 months. The analysis included both an assessment of the prosthesis as a unit and a separate evaluation of the individual components. Statistical analysis involved calculating sensitivity, specificity and accuracy using SPSS.Overall, a sensitivity of 77.8%, a specificity of 95.8% and an accuracy of 90.9% were found for detecting periprosthetic loosening, when considering the prosthesis as a unit. Individual component analyses showed a sensitivity of 71.4% and specificity of 96.2%.The use of [68Ga]Ga-DOTAZol PET/CT in periprosthetic loosening is a remarkable diagnostic tool and a promising approach. In comparison to established radionuclide tracers, 68Gallium-Zoledronate offers notable advantages due to its availability via 68Ge/68Ga-generators, improving its potential for clinical application.Conclusion: Periprosthetic loosening is a major complication after total hip and knee arthroplasty. Early and accurate diagnosis is essential to choose the right therapeutic path and to avoid further complications. The aim of the study was to evaluate the diagnostic performance of 68Gallium-Zoledronate ([68Ga]Ga-DOTAZol) PET/CT in detecting periprosthetic loosening in total hip (THA) and total knee arthroplasty (TKA).This retrospective study included 26 patients with painful prosthesis (THA n = 17; TKA n = 16) and clinical suspicion of periprosthetic loosening, but without a confirmed diagnosis. Patients underwent [68Ga]Ga-DOTAZol PET/CT at least one year post-implantation. Diagnosis was confirmed through revision surgery or long-term clinical follow-up, with an observation period of at least 6 months. The analysis included both an assessment of the prosthesis as a unit and a separate evaluation of the individual components. Statistical analysis involved calculating sensitivity, specificity and accuracy using SPSS.Overall, a sensitivity of 77.8%, a specificity of 95.8% and an accuracy of 90.9% were found for detecting periprosthetic loosening, when considering the prosthesis as a unit. Individual component analyses showed a sensitivity of 71.4% and specificity of 96.2%.The use of [68Ga]Ga-DOTAZol PET/CT in periprosthetic loosening is a remarkable diagnostic tool and a promising approach. In comparison to established radionuclide tracers, 68Gallium-Zoledronate offers notable advantages due to its availability via 68Ge/68Ga-generators, improving its potential for clinical application. [ABSTRACT FROM AUTHOR]