Preclinical Evaluation of Ac as a Theranostic Agent: Imaging, Dosimetry, and Therapy.

Ac (t = 29.37 h) has been proposed as a theranostic radioisotope leveraging both its diagnostic γ-emissions and therapeutic α-emissions. Ac emits 158 and 230 keV γ-photons ideal for quantitative SPECT imaging and acts as an in vivo generator of 4 high-energy α-particles.

Quantitative SPECT imaging of Tb and Tb for preclinical theranostic radiopharmaceutical development.

Background: Element-equivalent matched theranostic pairs facilitate quantitative in vivo imaging to establish pharmacokinetics and dosimetry estimates in the development of preclinical radiopharmaceuticals. Terbium radionuclides have significant potential as matched theranostic pairs for multipurpose applications in nuclear medicine. In particular, Tb (t = 5.

Preclinical evaluation of [Ac]Ac-crown-TATE - An alpha-emitting radiopharmaceutical for neuroendocrine tumors.

Background: Targeted alpha therapy (TAT) of somatostatin receptor-2 (SSTR2) positive neuroendocrine tumors (NETs) involving Ac-225 ([Ac]Ac-DOTA-TATE) has previously demonstrated improved therapeutic efficacy over conventional beta particle-emitting peptide receptor radionuclide therapy agents. DOTA-TATE requires harsh radiolabeling conditions for chelation of [Ac]Ac, which can limit the achievable molar activities and thus therapeutic efficacy of such TAT treatments. Macropa-TATE was recently highlighted as a potential alternative to DOTA-TATE, owing to the mild radiolabeling conditions and high affinity toward [Ac]Ac; however, elevated liver and kidney uptake were noted as a major limitation and a suitable imaging radionuclide is yet to be reported, which will be required for patient dosimetry studies and assessment of therapeutic benefit.

quantitative SPECT imaging of actinium-226: feasibility and proof-of-concept.

.Ac radiopharmaceuticals have tremendous potential for targeted alpha therapy, however,Ac (= 9.9 d) lacks direct gamma emissions forimaging.

Rearmed Bifunctional Chelating Ligand for Ac/Tb Precision-Guided Theranostic Radiopharmaceuticals─HnoneunpaX.

Superior bifunctional chelating ligands, which can sequester both α-emitting radionuclides (Ac, Bi) and their diagnostic companions (Tb, In), remain a formidable challenge to translating targeted alpha therapy, with complementary diagnostic imaging, to the clinic. HnoneupaX, a chelating ligand with an unusual diametrically opposed arrangement of pendant donor groups, has been developed to this end. HnoneunpaX preferentially complexes Ln and An ions, forming thermodynamically stable (pLa = 17.

Preclinical Evaluation of [Tb]Tb-Crown-TATE-A Novel SPECT Imaging Theranostic Agent Targeting Neuroendocrine Tumours.

Terbium radioisotopes (Tb, Tb, Tb, Tb) offer a unique class of radionuclides which encompass all four medicinally relevant nuclear decay modalities (α, , γ, /e), and show high potential for the development of element-matched theranostic radiopharmaceuticals. The goal of this study was to design, synthesise, and evaluate the suitability of crown-TATE as a new peptide-conjugate for radiolabelling of [Tb]Tb and [Tb]Tb, and to assess the imaging and pharmacokinetic properties of each radiotracer in tumour-bearing mice. [Tb]Tb-crown-TATE and [Tb]Tb-crown-TATE were prepared efficiently under mild conditions, and exhibited excellent stability in human serum (>99.

Toward Bifunctional Chelators for Thallium-201 for Use in Nuclear Medicine.

Auger electron therapy exploits the cytotoxicity of low-energy electrons emitted during radioactive decay that travel very short distances (typically <1 μm). Tl, with a half-life of 73 h, emits ∼37 Auger and other secondary electrons per decay and can be tracked as its gamma emissions enable SPECT imaging. Despite the useful nuclear properties of Tl, satisfactory bifunctional chelators to incorporate it into bioconjugates for molecular targeting have not been developed.

Hampa─Versatile Chelator for [Pb]Pb, [Bi]Bi, and [Ac]Ac.

A new decadentate chelator, Hampa, was designed to be a potential radiopharmaceutical chelator component. The chelator involves both amide and picolinate functional groups on a large non-macrocyclic, ether-bridged backbone. With its large scaffold, Hampa was paired with [Pb]Pb, [Bi]Bi, and La/[Ac]Ac ions.

Getting a lead on Pb-amide chelators for Pb radiopharmaceuticals.

Amide-based chelators DTPAm, EGTAm and ampam were synthesized to investigate which chelator most ideally coordinates [Pb]Pb ions for potential radiopharmaceutical applications. H NMR spectroscopy was used to study each metal-ligand complex in the solution state. The H NMR spectrum of [Pb(DTPAm)] revealed minimal isomerization and fluxional behaviour compared to [Pb(EGTAm)] and [Pb(ampam)], both of which showed fewer spectral changes indicative of less static behaviour.

Hhox: Rigid Cyclohexane-Reinforced Nonmacrocyclic Chelating Ligand for [Ga]Ga.

A rigid chiral acyclic chelator Hhox was synthesized and evaluated for Ga-based radiopharmaceutical applications; it was compared to the previously reported hexadentate Hhox to determine the effect of a backbone reinforced from adding a chiral 1S,2S-trans-cyclohexane on metal complex stability, kinetic inertness, and pharmacokinetics. NMR spectroscopy and theoretical calculation revealed that [Ga(hox)] showed a very similar coordination geometry to that of [Ga(hox)], and only one isomer in solution was observed by NMR spectroscopy. Solution studies showed that the modification results in a significant improvement in the exceptionally high thermodynamic stability of [Ga(hox)] with a 1.

Experimental and computational studies of Criegee intermediate reactions with NH and CHNH.

Ammonia and amines are emitted into the troposphere by various natural and anthropogenic sources, where they have a significant role in aerosol formation. Here, we explore the significance of their removal by reaction with Criegee intermediates, which are produced in the troposphere by ozonolysis of alkenes. Rate coefficients for the reactions of two representative Criegee intermediates, formaldehyde oxide (CH2OO) and acetone oxide ((CH3)2COO) with NH3 and CH3NH2 were measured using cavity ring-down spectroscopy.