Synthesis and Evaluation of a Bifunctional Chelator for Thorium-227 Targeted Radiotherapy.

Thorium-227 (Th) is an α-emitting radionuclide currently under investigation for targeted alpha therapy. Available chelators used for this isotope suffer from challenging multistep syntheses. Here, we present the synthesis and preclinical evaluation of a novel bifunctional chelator, SCN-Bn-DOTHOPO, which contains an isothiocyanate group that is suitable for conjugation to biological molecules.

Slow Magnetic Relaxation in a Californium Complex.

We report the synthesis and characterization of the macrocyclic californium derivative Na[Cf(HO)(DOTA)] (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate), , which was studied in comparison to its dysprosium counterpart, Na[Dy(HO)(DOTA)], . Divergent spectroscopic and magnetic behaviors were observed between and . Based upon spectroscopic measurements, we propose that accessible 5f → 6d transitions (potentially operating in tandem with charge-transfer transitions) are the major contributors to the observed broadband photoluminescence in .

Macrocyclic 1,2-Hydroxypyridinone-Based Chelators as Potential Ligands for Thorium-227 and Zirconium-89 Radiopharmaceuticals.

Thorium-227 (Th) is an α-emitting radionuclide that has shown preclinical and clinical promise for use in targeted α-therapy (TAT), a type of molecular radiopharmaceutical treatment that harnesses high energy α particles to eradicate cancerous lesions. Despite these initial successes, there still exists a need for bifunctional chelators that can stably bind thorium in vivo. Toward this goal, we have prepared two macrocyclic chelators bearing 1,2-hydroxypyridinone groups.

Siderocalin fusion proteins enable a new Y/Y theranostic approach.

The mammalian protein siderocalin binds bacterial siderophores and their iron complexes through cation-π and electrostatic interactions, but also displays high affinity for hydroxypyridinone complexes of trivalent lanthanides and actinides. In order to circumvent synthetic challenges, the use of siderocalin-antibody fusion proteins is explored herein as an alternative targeting approach for precision delivery of trivalent radiometals. We demonstrate the viability of this approach , using the theranostic pair Y (β, = 64 h)/Y (β, = 14.

Validation of a post-radiolabeling bioconjugation strategy for radioactive rare earth complexes with minimal structural footprint.

The nine-coordinate aza-macrocycle DO3Apic-NO2 and its kinetically inert rare earth complexes [M(DO3A-pic-NO2)]- (M = La, Tb, Eu, Lu, Y) can be readily bioconjugated to surface accessible thioles on peptides and proteins with a minimal structural footprint. All complexes express thioconjugation rate constants in the same order of magnitude ( = 0.3 h) with the exception of Sc ( = 0.

Accessing lanthanide-based, illuminated optical turn-on probes by modulation of the antenna triplet state energy.

Luminescent lanthanides possess ideal properties for biological imaging, including long luminescent lifetimes and emission within the optical window. Here, we report a novel approach to responsive luminescent Tb(iii) probes that involves direct modulation of the antenna excited triplet state energy. If the triplet energy lies too close to the D Tb(iii) excited state (20 500 cm), energy transfer to D competes with back energy transfer processes and limits lanthanide-based emission.

Multiplex and In Vivo Optical Imaging of Discrete Luminescent Lanthanide Complexes Enabled by In Situ Cherenkov Radiation Mediated Energy Transfer.

Recently, we pioneered the application of Cherenkov radiation (CR) of radionuclides for the in situ excitation of discrete Eu(III) and Tb(III) complexes. CR is produced by isotopes decaying under emission of charged particles in dielectric media and exhibits a maximum intensity below 400 nm. We have demonstrated that luminescent lanthanide antenna complexes are ideal acceptors for Cherenkov radiation-mediated energy transfer (CRET).

Evolution of Atomic-Level Structure in Sub-10 Nanometer Iron Oxide Nanocrystals: Influence on Cation Occupancy and Growth Rates.

Spinel iron oxide nanocrystals (NCs) have been reported to have atomic-level core and surface structural features that differ from those of the bulk material. Recent advances in a continuous growth synthesis of metal oxide NCs make it possible to prepare a series of NCs with subnanometer control of size with diameters below 10 nm that are well-suited for investigating size-dependent structure and reactivity. Here, we study the evolution of size-dependent structure in spinel iron oxide and determine how nanoscale structure influences the growth of NCs.

General Approach to Direct Measurement of the Hydration State of Coordination Complexes in the Gas Phase: Variable Temperature Mass Spectrometry.

The formation of ternary aqua complexes of metal-based diagnostics and therapeutics is closely correlated to their in vivo efficacy but approaches to quantify the presence of coordinated water ligands are limited. We introduce a general and high-throughput method for characterizing the hydration state of para- and diamagnetic coordination complexes in the gas phase based on variable-temperature ion trap tandem mass spectrometry. Ternary aqua complexes are directly observed in the mass spectrum and quantified as a function of ion trap temperature.

A High-Throughput Method To Measure Relative Quantum Yield of Lanthanide Complexes for Bioimaging.

Luminescent lanthanides provide a promising alternative to organic chromophores for cellular bioimaging and bioassay applications; efficacy is closely governed by their respective quantum yields. Conventionally utilized quantum-yield measurements for lanthanides are laborious and not amenable to rapid relative comparison of compound performance. Here, we introduce a high-throughput optical imaging method to determine and directly compare relative quantum yield using Cherenkov-radiation-mediated excitation of luminescent lanthanide complexes.

Cherenkov Radiation-Mediated In Situ Excitation of Discrete Luminescent Lanthanide Complexes.

Lanthanide luminescence, while ideal for in vivo applications owing to sharp emission bands within the optical window, requires high-intensity, short-wavelength excitation of small organic "antenna" chromophores in the vicinity of the lanthanide complex to access excited f-orbital states through intersystem crossing. Herein, we explored Cherenkov radiation of the radioisotopes F and Zr as an in situ source of antenna excitation. The effective inter- and intramolecular excitation of the terbium(III) complexes of a macrocylic polyaminocarboxylate ligand (hydration number (q)=0, quantum yield (φ)=47 %) as well as its analogue functionalized to append an intramolecular Cherenkov excitation source (q=0.