0000000000284974
AUTHOR
Konstantin Zhernosekov
Evaluation of Safety and Dosimetry of 177Lu-DOTA-ZOL for Therapy of Bone Metastases
Palliative treatment of bone metastasis using radiolabeled bisphosphonates is a well-known concept proven to be safe and effective. A new therapeutic radiopharmaceutical for bone metastasis is 177Lu-DOTA-zoledronic acid (177Lu-DOTA-ZOL). In this study, the safety and dosimetry of a single therapeutic dose of 177Lu-DOTA-ZOL were evaluated on the basis of a series of SPECT/CT images and blood samples. Methods: Nine patients with exclusive bone metastases from metastatic castration-resistant prostate cancer (mCRPC) (70.8 ± 8.4 y) and progression under conventional therapies participated in this prospective study. After receiving 5,780 ± 329 MBq 177Lu-DOTA-ZOL, patients underwent 3-dimensional …
The Szilard–Chalmers effect in macrocyclic ligands to increase the specific activity of reactor-produced radiolanthanides: Experiments and explanations
Abstract Successful utilization of medical isotopes in the radiolabeling reactions to a significant degree depends on the technically achievable specific activity. In this respect, the Szilard-Chalmers effect is considered in detail as a radiochemical tool to increase the specific activity of radionuclides produced by direct nuclear reactions. In the present study, a physico-chemical model is described utilizing the specific aspects of thermodynamically and kinetically stabilised metal-ligand complexes. The approach is applied as a proofof- principle study to increase the specific activity of 166Ho, produced via the (n, γ) nuclear reaction. As a target material, 165Ho-DOTA is used. In this …
Processing of Generator-Produced 68Ga for Medical Application
The (68)Ge/(68)Ga generator provides an excellent source of positron-emitting (68)Ga. However, newly available "ionic" (68)Ge/(68)Ga radionuclide generators are not necessarily optimized for the synthesis of (68)Ga-labeled radiopharmaceuticals. The eluates have rather large volumes, a high concentration of H(+) (pH of 1), a breakthrough of (68)Ge, increasing with time or frequency of use, and impurities such as stable Zn(II) generated by the decay of (68)Ga, Ti(IV) as a constituent of the column material, and Fe(III) as a general impurity.We have developed an efficient route for the processing of generator-derived (68)Ga eluates, including the labeling and purification of biomolecules. Prec…
Complex formation of Tb3+ with glycolate, D-gluconate and α-isosaccharinate in neutral aqueous perchlorate solutions
Summary An electromigration technique was used for measurements of metal-ligand formation constants of non-carrier-free 160Tb3+ with glycolate, D-gluconate and α-isosaccharinate ligands. The overall ion mobilities of Tb at different concentrations of the ligands were measured in chemically inert perchlorate solutions (pH 7 and T= 298.1K) with an overall ionic strength μ = 0.1. The stepwise stoichiometric stability constants are: Tb3+/glycolate: log K 1=2.72(18), log K 2=1.73(19), log K 3= 1.12(17), Tb3+/D-gluconate: log K 1=2.96(11), log K 2=2.60(11), log K 3=1.13(9), Tb3+/α-ISA: log K 1=3.07(8), log K 2 = 2.69(11), log K 3 = 1.80(12).
Comparison of different phosphorus-containing ligands complexing 68Ga for PET-imaging of bone metabolism
Abstract 99mTc-phosphonate structures are well established tracers for bone tumour imaging. Our objective was to investigate different 68Ga-labelled phosphonate ligands concerning labelling kinetics, binding to hydroxyapatite and bone imaging using μ-PET. Seven macrocyclic phosphorus-containing ligands and EDTMP were labelled in nanomolar scale with n.c.a. 68Ga in Na-HEPES buffer at pH∼4. Except for DOTP, all ligands were labelled with >92% yield. Binding of the 68Ga-ligand complexes on hydroxyapatite was analysed to evaluate the effect of the number of the phosphorus acid groups on adsorption parameters. Adsorption of 68Ga-EDTMP and 68Ga-DOTP was >83%. For the 68Ga-NOTA-phosphonates …
Limiting transport properties of lanthanide and actinide ions in pure water
Summary The limiting transport properties, i.e. the limiting ionic conductivity (λ°) and the limiting diffusion coefficient (D°), of lanthanide and actinide ions at 298.15K have been calculated by means of the microscopic version of the Stokes–Einstein law involving (i) the effective charge and the ionic radius of the ions and (ii) the ion micro-viscosity, i.e. the viscosity of the hydrated water molecules in the vicinity of the ion. The latter quantity was derived from the variation of the dynamic properties of the water molecules in the first hydration shell with the surface charge density of common mono-atomic cations of various charges. The obtained results were found to be consistent w…
Development of a [177Lu]BPAMD Labeling Kit and an Automated Synthesis Module for Routine Bone Targeted Endoradiotherapy
Painful bone lesions, both benign and metastatic, are often managed using conventional analgesics. However, the treatment response is not immediate and is often associated with side-effects. Radionuclide therapy is used for pain palliation in bone metastases as well as some benign neoplasms. Endoradiotherapy has direct impact on the pain-producing bone elements, and hence, response is significant, with minimal or no side-effects. A new potential compound for endoradiotherapy is [(177)Lu]BPAMD. It combines a highly affine bisphosphonate, covalently bridged with DOTA through an amide bond, with the low-energy β(-) emitting therapeutic radiolanthanide (177)Lu. For routine chemical application,…
Improved column-based radiochemical processing of the generator produced 68Ga.
An improved chemical strategy for processing of the generator produced (68)Ga was developed based on processing of the original (68)Ge/(68)Ga generator eluate on a micro-column. Direct pre-concentration and purification of the eluted (68)Ga is performed on a cation-exchange resin in hydrochloric acid/acetone media. A supplementary step based on a second micro-column filled with a second resin allows direct re-adsorption of (68)Ga eluted from the cation exchanger. (68)Ga is finally striped from the second resin with a small volume of pure water. For this purpose a strong anion exchanger and a novel extraction chromatographic resin based on tetraalkyldiglycolamides are characterized. The stra…