Nowadays, PSMA ligands are widely used for radiotheragnostic purposes in prostate cancer. The synthesis of a PSMA-Bisp conjugate was developed and realized with good yield (overall yield ~58% for the last two steps). All newly synthesized compounds were characterized by physicochemical methods: 1H and 13C NMR, HRMS, and LCMS (for biologically tested samples). Subsequently, Bisp1 (diacetate bispidine ligand), Bisp-alkyne (bifunctional derivative of Bisp1), and its conjugate PSMA-Bisp were labeled by 64Cu in mild conditions. In vitro studies of the labeled conjugate [64Cu]Cu-PSMA-Bisp have shown great stability in model solutions. Finally, [64Cu]Cu-PSMA-Bisp was compared to the well-known PSMA-617 conjugate labeled with 64Cu and they showed similar stability in excess bovine serum (BVS), and at the same time, labeling PSMA-Bisp with 64Cu is characterized by extremely high kinetics in mild conditions, while labeling PSMA-617 with 64Cu requires heating (90 °C). Thus, this conjugate can be incredibly promising for nuclear medicine.

In this article, we present the synthesis and characterization of new acyclic pyridine-containing polyaminocarboxylate ligands H4aPyta and H6aPyha, which differ in structural rigidity and the number of chelating groups. Their abilities to form complexes with Cu2+, Ga3+, Y3+, and Bi3+ cations, as well as the stability of the complexes, were evaluated by potentiometric titration method, radiolabeling with the corresponding radionuclides, in vitro studies, mass spectrometry, and HPLC. The structures of the resulting complexes were determined using NMR spectroscopy and DFT calculations. The results obtained made it possible to evaluate the influence of the structural features of the complexes on their stability. The developed chelators H4aPyta and H6aPyha were proved to be promising for further research in the field of radiopharmaceuticals.

Nowadays PSMA ligands are widely used for radiotheragnostic purposes of prostate cancer. The goal of this study was to synthesize and estimate stability in vitro of copper complex with diacetate bispidine ligand (Bisp1), its bifunctional derivative (Bisp-alkyne) and its conjugate – bispidine-PSMA ligand (PSMA-Bisp) to evaluate the possibility of applying one as radiotheragnostic agent. The synthesis for PSMA-Bisp conjugate was developed and realized with good yields. All newly synthesized compounds were characterized by a set of physicochemical methods: 1H and 13C NMR, HRMS and LCMS (for final molecules). Subsequently, Bisp1 and Bisp-alkyne and its derivative PSMA-Bisp were labelled by 64Cu at mild conditions. In vitro studies of the labelled conjugate [64Cu]Cu-PSMA-Bisp have shown the great stability in model solutions. Finally, [64Cu]Cu-PSMA-Bisp was compared to well-known PSMA-617 conjugate labelled with 64Cu and they have showed similar stability in excess of bovine serum (BVS), and at the same time labelling PSMA-Bisp with 64Cu is characterized by extremely high kinetics at mild conditions, while labeling PSMA-617 with 64Cu requires heating (90 °C) [PMCID: PMC5435610]. Thus, the conjugate PSMA-Bisp could be promising candidate for further investigations expanded in vitro and in vivo investigations.

Thz-Phe-D-Trp-Lys-Thr-DOTA, a conjugate of the DOTA chelator and the Thz-Phe-D-Trp-Lys-Thr pentapeptide, was labeled with 152Eu and 161Tb radionuclides, where 161Tb has decay characteristics suitable for its use in cancer therapy. For the [152Eu]Eu-Thz-Phe-D-Trp-Lys-Thr-DOTA complex, the biodistribution in nude mice bearing IMR-32 tumors was evaluated for the first time. It was shown that the complexes of the conjugate demonstrate accumulation in the tumor at the level of DOTA-TATE, another peptide conjugate widely used in nuclear medicine for the diagnosis and therapy of neuroendocrine tumors, which allows Thz-Phe-D-Trp-Lys-Thr-DOTA to be considered as a potential biological vector for radiopharmaceuticals.

A synthetic procedure for the synthesis of azacrown ethers with a combination of pendant arms has been developed and the synthesized ligand, characterized by various techniques, was studied. The prepared benzoazacrown ether with hybrid pendant arms and its complexes with copper and lead cations were studied in terms of biomedical applications. Similarly to a fully acetate analog, the new one binds both cations with close stability constants, despite the decrease in both constants. The calculated geometry of the complexes correlate with the data from X-ray absorption and NMR spectroscopy. Coordination of both cations differs due to the difference between the ionic radii. However, these chelation modes provide effective shielding of cations in both cases, that was shown by the stability of their complexes in the biologically relevant media towards transchelation and transmetallation.

Using a mouse model, an organ distribution for microgels of carboxymethyl cellulose cross-linked with 67Cu2+ ions was investigated and compared with the distribution of free 67Cu2+ ions from 67CuCl2. The clearance of the microgels through both liver and kidneys was demonstrated. An additional examination of distribution for [3H]CMC microparticles and [3H]CMC–Cu microgels revealed no copper release from the microgels in vivo.

In this work we presented a synthesis and investigation of relative acyclic and macrocyclic polyamines with picolinate pendant arms as potential chelators for copper radiopharmaceuticals. It has been shown that linear chelators lacking bisamide moiety are much more basic and form complexes with higher stability constants compared to macrocyclic ones. Both types of ligands possess many donor sites due to picolinate groups enabling formation of polynuclear complexes in the solution and solid state. According to crystal structures metal cations coordinates with studied ligands through the binding with aminogroups and picolinates donor atoms, while terminal aminogroups of acyclic ligands do not take part in the complex formation. Tripicolinate azacrown ligand coordinates cations outside the macrocyclic cavity in non-equivalent positions. However this out-cage location as well as a moderate logK value do not induce fast release of cation from this complex in the challenging medium of serum proteins.

Copper-based radiopharmaceuticals are of high interest these days owing to the decay properties of copper radioisotopes. In contrast, labeled zinc compounds have been less studied for applications in nuclear medicine. In this study, the stability of labeled zinc and copper complexes with two azacrown ether ligands was investigated and compared. Then, the in vitro and in vivo stability of the studied zinc complexes was demonstrated, with the complexes showing promise for biomedical applications. In contrast, analogous copper complexes quickly dissociated in the presence of serum proteins. Furthermore, a simple method for the production of radiochemically pure Zn-65 was proposed, and the opportunity for its use as a surrogate radionuclide for research into potential zinc-containing radiopharmaceuticals was demonstrated.

Formation of Sc radioisotopes under the irradiation of titanium of natural isotopic composition by bremsstrahlung photons with energies up to 55 MeV was studied. The yield of 47Sc is 5·105 Bq/μA h (g/cm2). Inevitable impurities are 46Sc and 48Sc (1.5% and 9.1% of 47Sc radioactivity at EOB, respectively). 47Sc was separated by extraction chromatography on a DGA resin in HNO3 and HCl media. The separation procedure takes about 2 h, the radiochemical efficiency was > 97%. The result was compared with other photonuclear experiments on titanium nuclei. It is shown that the photonuclear method can be used for the production of therapeutic amounts of 47Sc.

Production of medical radionuclide 67 Cu by the irradiation of Zn of natural isotopic composition by bremsstrahlung photons of maximum energy of 55 MeV was studied. Production yields of 67 Cu and other activation products were determined. The yield of 67 Cu is (2.34 ± 0.07) × 10 5 Bq/(μA h g/cm 2 ) at EOB. The experimental data were compared with the results of other experiments and theoretical calculations based on the statistical model in the TALYS software and on the combined model of photonuclear reactions. Technique of chemical separation of 67 Cu from irradiated zinc target based on extraction chromatography using CU Resin was applied. Radiochemical yield was > 95%, separation time was 1 h. The possibility of production of medical quantities was discussed.

In this work, the separation of 89Zr, a radionuclide promising for positron-emission tomography, from an irradiated yttrium target using different extraction-chromatographic resins (TEVA, UTEVA, TRU, and LN resins ©Triskem) was studied. Distribution coefficients of Zr(IV) onto TEVA, LN (in HCl solutions), and onto TRU (in HCl and HNO3) were determined. The optimum conditions for the separation of Zr(IV) and Y(III) using these resins were proposed. In each case, the maximum separation factor was higher than 105. The developed separation procedures allow to obtain 89Zr of high radiochemical purity for dilute mineral acids.

Abstract A method for obtaining 156, 155, 154m2, 154, 153Tb radiotracers by the irradiation of a europium oxide target of natural isotopic composition by 27 MeV α-particles is proposed. Terbium can be efficiently separated from bulk of europium by the reduction of the latter by zinc in an acidic solution and precipitation as EuSO4. The optimum Zn/Eu3+ and (NH4)2SO4/Eu3+ molar ratios are 20 and 3, respectively. Terbium is additionally purified from europium and gadolinium by extraction chromatography using LN Resin. It is demonstrated that optimum separation is attained in 0.6 M HNO3. The Tb/Eu separation coefficient was ~5·105. The yield of terbium was about 90%. Time of all steps was 1.5–2 h. The proposed procedure makes it possible to obtain no carrier added terbium radiotracers.