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BackgroundThe targeting of the prostate-specific membrane antigen (PSMA) is of particular interest for radiotheragnostic purposes of prostate cancer. Radiolabeled PSMA-617, a 1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA)-functionalized PSMA ligand, revealed favorable kinetics with high tumor uptake, enabling its successful application for PET imaging (68Ga) and radionuclide therapy (177Lu) in the clinics. In this study, PSMA-617 was labeled with cyclotron-produced 44Sc (T 1/2 = 4.04 h) and investigated preclinically for its use as a diagnostic match to 177Lu-PSMA-617.Results 44Sc was produced at the research cyclotron at PSI by irradiation of enriched 44Ca targets, followed by chromatographic separation. 44Sc-PSMA-617 was prepared under standard labeling conditions at elevated temperature resulting in a radiochemical purity of >97% at a specific activity of up to 10 MBq/nmol. 44Sc-PSMA-617 was evaluated in vitro and compared to the 177Lu- and 68Ga-labeled match, as well as 68Ga-PSMA-11 using PSMA-positive PC-3 PIP and PSMA-negative PC-3 flu prostate cancer cells. In these experiments it revealed similar in vitro properties to that of 177Lu- and 68Ga-labeled PSMA-617. Moreover, 44Sc-PSMA-617 bound specifically to PSMA-expressing PC-3 PIP tumor cells, while unspecific binding to PC-3 flu cells was not observed. The radioligands were investigated with regard to their in vivo properties in PC-3 PIP/flu tumor-bearing mice. 44Sc-PSMA-617 showed high tumor uptake and a fast renal excretion. The overall tissue distribution of 44Sc-PSMA-617 resembled that of 177Lu-PSMA-617 most closely, while the 68Ga-labeled ligands, in particular 68Ga-PSMA-11, showed different distribution kinetics. 44Sc-PSMA-617 enabled distinct visualization of PC-3 PIP tumor xenografts shortly after injection, with increasing tumor-to-background contrast over time while unspecific uptake in the PC-3 flu tumors was not observed.ConclusionsThe in vitro characteristics and in vivo kinetics of 44Sc-PSMA-617 were more similar to 177Lu-PSMA-617 than to 68Ga-PSMA-617 and 68Ga-PSMA-11. Due to the almost four-fold longer half-life of 44Sc as compared to 68Ga, a centralized production of 44Sc-PSMA-617 and transport to satellite PET centers would be feasible. These features make 44Sc-PSMA-617 particularly appealing for clinical application.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-017-0257-4) contains supplementary material, which is available to authorized users.

These human data demonstrate that surgical trauma is followed by resident muscularis macrophage activation and the upregulation, release, and functional activity of proinflammatory cytokines and kinetically active mediators.

In recent years, 47 Sc has attracted attention because of its favorable decay characteristics (half-life, 3.35 d; average energy, 162 keV; Eγ, 159 keV) for therapeutic application and for SPECT imaging. The aim of the present study was to investigate the suitability of 47 Sc for radionuclide therapy in a preclinical setting. For this purpose a novel DOTA-folate conjugate (cm10) with an albumin-binding entity was used. Methods: 47 Sc was produced via the 46 Ca(n,γ) 47 Ca! b − 47 Sc nuclear reaction at the high-flux reactor at the Institut Laue-Langevin. Separation of the 47 Sc from the target material was performed by a semi-automated process using extraction chromatography and cation exchange chromatography. 47 Sc-labeled cm10 was tested on folate receptor-positive KB tumor cells in vitro. Biodistribution and SPECT imaging experiments were performed in KB tumor-bearing mice. Radionuclide therapy was conducted with two groups of mice, which received either 47 Sc-cm10 (10 MBq) or only saline. Tumor growth and survival time were compared between the two groups of mice. Results: Irradiation of 46 Ca resulted in approximately 1.8 GBq of 47 Ca, which subsequently decayed to 47 Sc. Separation of 47 Sc from 47 Ca was obtained with 80% yield in only 10 min. The 47 Sc was then available in a small volume (∼500 μL) of an ammonium acetate/HCl (pH 4.5) solution suitable for direct radiolabeling. 47 Sc-cm10 was prepared with a radiochemical yield of more than 96% at a specific activity of up to 13 MBq/nmol. In vitro 47 Sccm10 showed folate receptor-specific binding and uptake into KB tumor cells. In vivo SPECT/CT images allowed the visualization of accumulated radioactivity in KB tumors and in the kidneys. The therapy study showed a significantly delayed tumor growth in mice, which received 47 Sc-cm10 (10 MBq, 10 Gy) resulting in a more than 50% increase in survival time, compared with untreated control mice. Conclusion: With this study, we demonstrated the suitability of using 47 Sc for therapeutic purposes. On the basis of our recent results obtained with 44 Sc-folate, the present work confirms the applicability of 44 Sc/ 47 Sc as an excellent matched pair of nuclides for PET imaging and radionuclide therapy.

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SPECT/CT significantly improved the specificity and positive predictive value of bone scintigraphy in cancer patients. In breast cancer patients, we found a slight increase in sensitivity. SPECT/CT had a significant effect on clinical management because of correct downstaging and upstaging, better definition of the extent of metastases, and a reduction in further diagnostic procedures.

Studies of the halide complexation of element 105 in aqueous solution were performed on 34-s 262 Ha produced in the 249 Bk( ls O,5n) reaction. The 262 Ha was detected by measuring the fission and alpha activities associated with its decay and the alpha decays of its daughter, 4.3-s 258 Lr. Time-correlated pairs of parent and daughter alpha particles provided a unique identification of the presence of 262 Ha. About 1600 anion exchange separations of 262 Ha from HCl and mixed HC1/HF solutions were performed on a one-minute time scale. Reversed-phase micro-chromatographic columns incorporating triisooctyl amine (TIOA) on an inert support were used in the computer-controlled liquid chromatography apparatus, ARCA II. -.