Synthesis and preclinical evaluation of DOTAGA-conjugated PSMA ligands for functional imaging and endoradiotherapy of prostate cancer
Due to its high expression in prostate cancer, PSMA (prostate-specific membrane antigen) represents an ideal target for both diagnostic imaging and endoradiotherapeutic approaches. Based on a previously published highly specific PSMA ligand ([(68)Ga]DOTA-FFK(Sub-KuE)), we developed a corresponding metabolically stable 1,4,7,10-tetraazacyclododececane,1-(glutaric acid)-4,7,10-triacetic acid (DOTAGA) construct for theranostic treatment of prostate cancer. All ligands were synthesized by a combined solid phase and solution phase synthesis strategy…
Tailored Gallium(III) Chelator NOPO: Synthesis, Characterization, Bioconjugation, and Application in Preclinical Ga-68-PET Imaging
The bifunctional chelator NOPO (1,4,7-triazacyclononane-1,4-bis[methylene(hydroxyl-methyl)phosphinic acid]-7-[methylene(2-carboxyethyl)phosphinic acid]) shows remarkably high GaIII complexation efficiency and comprises one carboxylic acid moiety which is not involved into metal ion coordination. An improved synthetic protocol affords NOPO with 45% overall yield. Stepwise protonation constants (log Ka), determined by potentiometry, are 11.96, 5.22, 3.77,...
A facile direct nucleophilic synthesis of O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) without HPLC purification
Due to favourable in vivo characteristics, its high specificity and the longer half-life of 18F (109.8 min) allowing for remote-site delivery, O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) has gained increased importance for molecular imaging of cerebral tumors. Consequently, the development of simple and efficient production strategies for [18F]FET could be an important step to further improve the cost-effective availability of [18F]FET in the clinical environment. In the present study [18F]FET ...
Phosphinic Acid Functionalized Polyazacycloalkane Chelators for Radiodiagnostics and Radiotherapeutics: Unique Characteristics and Applications
Given the wide application of positron emission tomography (PET), positron-emitting metal radionuclides have received much attention recently. Of these, gallium-68 has become particularly popular, as it is the only PET nuclide commercially available from radionuclide generators, therefore allowing local production of PET radiotracers independent of an on-site cyclotron.
Benefits of NOPO As Chelator in Gallium-68 Peptides, Exemplified by Preclinical Characterization of 68Ga-NOPO–c(RGDfK)
The αvβ3-integrin addressing cyclic pentapeptide cyclo(RGDfK) was conjugated to NOPO, 1,4,7-triazacyclononane-1,4-bis[methylene(hydroxymethyl)phosphinic acid]-7-[methylene(2-carboxyethyl)phosphinic acid], a bifunctional chelator with exceptional gallium-68 labeling properties. NOPO–c(RGDfK) and its Ga(III) and Cu(II) complexes showed high affinity to αvβ3integrin (IC50 = 0.94 ± 0.06, 1.02 ± 0.09, and 0.51 ± 0.06 nM, respectively).