Cyclohexanediamine Triazole (CHDT) Functionalization Enables Labeling of Target Molecules with AlF/Ga/In.

The AlF-labeling approach offers a one-step access to radiofluorinated biomolecules by mimicking the labeling process for radiometals. Although these labeling conditions are considered to be mild compared to classic radiofluorinations, improvements of the chelating units have led to the discovery of , which allows AlF-labeling already at ambient temperature. While the suitability of for functionalization and radiofluorination of proteins is well established, its use for small molecules or peptides is less explored.

Scalability study on [La]LaCl production with a focus on potential clinical applications.

Background: In recent years, targeted alpha therapy has gained importance in the clinics, and in particular, the alpha-emitter Ac plays a fundamental role in this clinical development. Nevertheless, depending on the chelating system no real diagnostic alternative has been established which shares similar chemical properties with this alpha-emitting radionuclide. In fact, the race to launch a diagnostic radionuclide to form a matched pair with Ac is still open, and La features attractive radiation properties to claim this place.

Production of the PET radionuclide Cu via the Ni(p,2n)Cu nuclear reaction.

Background: There are only a handful of true theranostic matched pairs, and in particular the theranostic radiocopper trio Cu, Cu and Cu, for diagnosis and therapy respectively, is a very attractive candidate. In fact, the alternative of two imaging radionuclides with different half-lives is a clear advantage over other theranostic pairs, since it offers a better matching for the tracer biological and radionuclide physical half-lives. Due to the high availability of Cu, its translation into the clinic is being successfully carried out, giving the example of the FDA approved radiopharmaceutical Detectnet (copper Cu 64 dotatate injection).

Bispidine Chelators for Radiopharmaceutical Applications with Lanthanide, Actinide, and Main Group Metal Ions.

Octadentate and specifically nonadentate ligands with a bispidine scaffold (3,7-diazabicyclo[3.3.1]nonane) are known to be efficiently coordinated to a range of metal ions of interest in radiopharmaceutical chemistry and lead to exceedingly stable and inert complexes.

Financial recommendations on Reddit, stock returns and cumulative prospect theory.

This study investigates stock recommendations from the three largest finance subreddits on Reddit: wallstreetbets, investing and stocks. A simple strategy that buys recommended stocks weighted by the number of posts per day yields a portfolio with higher average returns at the expense of higher risks than the market for all holding periods, i.e.

Cyclotron-Based Production of Cu for Radionuclide Theranostics via the Zn(p,α)Cu Reaction.

Theranostic matched pairs of radionuclides have aroused interest during the last couple of years, and in that sense, copper is one element that has a lot to offer, and although Cu and Cu are slowly being established as diagnostic radionuclides for PET, the availability of the therapeutic counterpart Cu plays a key role for further radiopharmaceutical development in the future. Until now, the Cu shortage has not been solved; however, different production routes are being explored. This project aims at the production of no-carrier-added Cu with high radionuclidic purity with a medical 30MeV compact cyclotron via the Zn(p,α)Cu reaction.

Efficient Production of the PET Radionuclide La for Theranostic Purposes in Targeted Alpha Therapy Using the Ba(p,2n)La Reaction.

Targeted Alpha Therapy is a research field of highest interest in specialized radionuclide therapy. Over the last decades, several alpha-emitting radionuclides have entered and left research topics towards their clinical translation. Especially, 225Ac provides all necessary physical and chemical properties for a successful clinical application, which has already been shown by [225Ac]Ac-PSMA-617.

Cyclam with a phosphinate-bis(phosphonate) pendant arm is a bone-targeting carrier of copper radionuclides.

Ligands combining a bis(phosphonate) group with a macrocycle function as metal isotope carriers for radionuclide-based imaging and for treating bone metastases associated with several cancers. However, bis(phosphonate) pendant arms often slow down complex formation and decrease radiochemical yields. Nevertheless, their negative effect on complexation rates may be mitigated by using a suitable spacer between bis(phosphonate) and the macrocycle.

Radiolabelled Cyclic Bisarylmercury: High Chemical and in vivo Stability for Theranostics.

We show the synthesis of an in vivo stable mercury compound with functionality suitable for radiopharmaceuticals. The designed cyclic bisarylmercury was based on the water tolerance of organomercurials, higher bond dissociation energy of Hg-Ph to Hg-S, and the experimental evidence that acyclic structures suffer significant cleavage of one of the Hg-R bonds. The bispidine motif was chosen for its in vivo stability, chemical accessibility, and functionalization properties.

Recent Insights in Barium-131 as a Diagnostic Match for Radium-223: Cyclotron Production, Separation, Radiolabeling, and Imaging.

Barium-131 is a single photon emission computed tomography (SPECT)-compatible radionuclide for nuclear medicine and a promising diagnostic match for radium-223/-224. Herein, we report on the sufficient production route Cs(,)Ba by using 27.5 MeV proton beams.

Cation Exchange Protocols to Radiolabel Aqueous Stabilized ZnS, ZnSe, and CuFeS Nanocrystals with Cu for Dual Radio- and Photo-Thermal Therapy.

Here, cation exchange (CE) reactions are exploited to radiolabel ZnSe, ZnS, and CuFeS metal chalcogenide nanocrystals (NCs) with Cu. The CE protocol requires one simple step, to mix the water-soluble NCs with a Cu solution, in the presence of vitamin C used to reduce Cu(II) to Cu(I). Given the quantitative cation replacement on the NCs, a high radiochemical yield, up to 99%, is reached.

Dual-time-point Cu-PSMA-617-PET/CT in patients suffering from prostate cancer.

Regardless of its high positron energy, Ga-labeled PSMA ligands have become standard of care in metabolic prostate cancer imaging. Cu, a radionuclide with a much longer half-life (12.7 h), is available for PSMA labeling allowing imaging much later than Ga.

Radiochemical and radiopharmacological characterization of a Cu-labeled α-MSH analog conjugated with different chelators.

Radiolabeled α-melanocyte-stimulating hormone (α-MSH) derivatives have a high potential for diagnosis and treatment of melanoma, because of high specificity and binding affinity to the melanocortin-1 receptor (MC1R). Hence, the α-MSH-derived peptide NAP-NS1 with a β-Ala linker (ε-Ahx-β-Ala-Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH ) was conjugated to different chelators: either to NOTA (p-SCN-Bn-1,4,7-triazacyclononane-1,4,7-triacetic acid), to a hexadentate bispidine carbonate derivative (dimethyl-9-(((4-nitrophenoxy)carbonyl)oxy)-2,4-di(pyridin-2-yl)-3,7-bis(pyridin-2-ylmethyl)-3,7-diazabicyclo[3.3.

Molecular imaging using the theranostic agent Hg: phantom measurements and Monte Carlo simulations.

Background: Radiomercury Hg and Hg, henceforth referred to as Hg, is a promising theranostic radionuclide endowed with properties that allow diagnostic and therapeutic applications. The aim of this work was to investigate the capabilities of Hg for nuclear medicine imaging. Therefore measurements were performed by using a Philips BrightView SPECT camera.

Exploring pitfalls of Cu-labeled EGFR-targeting peptide GE11 as a potential PET tracer.

The epidermal growth factor receptor (EGFR) represents an important molecular target for both radiotracer-based diagnostic imaging and radionuclide therapy of various cancer entities. For the delivery of radionuclides to the tumor, peptides hold great potential as a transport vehicle. With respect to EGFR, the peptide YHWYGYTPQNVI (GE11) has been reported to bind the receptor with high specificity and affinity.

Novel Tumor Pretargeting System Based on Complementary l-Configured Oligonucleotides.

Unnatural mirror image l-configured oligonucleotides (L-ONs) are a convenient substance class for the application as complementary in vivo recognition system between a tumor specific antibody and a smaller radiolabeled effector molecule in pretargeting approaches. The high hybridization velocity and defined melting conditions are excellent preconditions of the L-ON based methodology. Their high metabolic stability and negligible unspecific binding to endogenous targets are superior characteristics in comparison to their d-configured analogs.

Drug resistance of clinical varicella-zoster virus strains confirmed by recombinant thymidine kinase expression and by targeted resistance mutagenesis of a cloned wild-type isolate.

In this study, approaches were developed to examine the phenotypes of nonviable clinical varicella-zoster virus (VZV) strains with amino acid substitutions in the thymidine kinase (TK) (open reading frame 36 [ORF36]) and/or DNA polymerase (Pol) (ORF28) suspected to cause resistance to antivirals. Initially, recombinant TK proteins containing amino acid substitutions described as known or suspected causes of antiviral resistance were analyzed by measuring the TK activity by applying a modified commercial enzyme immunoassay. To examine the effects of these TK and Pol substitutions on the replication of recombinant virus strains, the method of en passant mutagenesis was used.

Theranostic mercury: (197(m))Hg with high specific activity for imaging and therapy.

The no carrier added (NCA) radionuclide (197(m))Hg is accessible through proton induced nuclear reactions on gold. The decay properties of both simultaneous produced nuclear isomers (197m)Hg and (197)Hg like convenient half life, low energy gamma radiations for imaging, Auger and conversion electrons for therapy are combined with unique chemical and physical properties of mercury and its compounds. Gold as a monoisotopic element has a natural abundance of 100% (197)Au superseding expensive enrichment for the target material.

Bispidines for dual imaging.

The efficient transformation of the hexadentate bispidinol 1 into carbamate derivatives yields functional bispidines enabling convenient functionalization for targeted imaging. The BODIPY-substituted bispidine 3 combines a coordination site for metal ions, such as radioactive (64) Cu(II) , with a fluorescent unit. Product 3 was thoroughly characterized by standard analytical methods, single crystal X-ray diffraction, radiolabeling, and photophysical analysis.

High specific activity ⁶¹Cu via ⁶⁴Zn(p,α)⁶¹Cu reaction at low proton energies.

The PET radionuclide (61)Cu is accessible through several nuclear reactions. Besides the common production route via (61)Ni(p,n)(61)Cu the (64)Zn(p,α)(61)Cu reaction offers some advantages. Especially the comparatively cheap enriched (64)Zn makes this process economical.

Impact of functionalized coligands on the pharmacokinetics of 99mTcIII '4+1' mixed-ligand complexes conjugated to bombesin.

Bombesins (BN) containing (99m)Tc '4+1' complexes may be useful to detect tumors expressing the gastrin-releasing peptide receptor (GRPR). Derivatives of the formula [(99m)Tc(NS(3)R)(L2-BN(st))] were synthesized, in which Tc(III) is coordinated by an isocyanide L2-BN(st) bearing the peptide (BN(st)=βAla-βAla-Gln-Trp-Ala-Val-Gly-His-Cha-Nle-NH(2)) and a tetradentate chelator NS(3)R. NS(3)R consists of 2,2',2″-nitrilotriethanethiol (NS(3)) bearing a crown ether (NS(3)crown), an aliphatic amine (NS(3)en) and a tricarboxylic acid (NS(3)(COOH)(3)).

Implementation of 89Zr production and in vivo imaging of B-cells in mice with 89Zr-labeled anti-B-cell antibodies by small animal PET/CT.

We examined the production, separation, and characterization of (89)Zr, including supplementation of a commercial Cyclone(®) 18/9 with a self-made Solid Target System (STS). Obtained [(89)Zr]Zr-oxalate was used for the labeling of anti-B cell antibodies with desferrioxamine-p-SCN as a bifunctional chelator. (89)Zr-labeled antibodies were injected in DBA/1 mice to examine usability for detection of B cells in vivo.

Novel 99mTc '4 + 1' peptide conjugates: tuning the biodistribution by variation of coligands.

A sophisticated coligand strategy is presented for peptide-derived radioconjugates based on (99m)Tc '4 + 1' mixed-ligand complexes. The new pharmacologically active coligands are assessed for (99m)Tc-labeling of the RGD-peptide cyclo(Arg-Gly-Asp-D-Tyr-Lys) which is an established vehicle to target alpha(v)beta(3) integrins playing a crucial part in tumor pathogenesis. Complexes of the general formula [(99m)Tc(NS(3)R)X] were synthesized and evaluated, in which Tc(III) is coordinated by NS(3)R, a derivative of the tetradentate chelator 2,2',2''-nitrilotriethanethiol (NS(3)), and by X, a monodentate binding isocyanide bearing the biomolecule.

Validation of (99m)Tc-labeled "4+1" fatty acids for myocardial metabolism and flow imaging: Part 2. Subcellular distribution.

Introduction: Our group has synthesized technetium-labeled fatty acids (FA) that are extracted into the myocardium and sequestered due to heart-type fatty acid binding protein (H-FABP) binding. In this article, we further address the detailed subcellular distribution and potential myocardial metabolism of [(99m)Tc]"4+1" FA.

Methods: Experiments were conducted using isolated hearts of Wistar rats, as well as of wild-type and H-FABP(-/-) mice.

Validation of (99m)Tc-labeled "4+1" fatty acids for myocardial metabolism and flow imaging: Part 1: myocardial extraction and biodistribution.

Introduction: (13)C, (18)F and (123)I fatty acids (FA) are used for myocardial imaging. Recently, our group showed that [(99m)Tc]-labeled "4+1" FA are extracted into the rat and guinea pig myocardium. The present study evaluates determinants of myocardial uptake and whole body biodistribution of these FA derivatives.