Synthesis and Characterization of Thallium-Texaphyrin Nanoparticles and Their Assessment as Potential Delivery Systems for Auger Electron-Emitting Tl to Cancer Cells.

Thallium-201 is an Auger electron-emitting radionuclide with significant potential for targeted molecular radiotherapy of cancer. It stands out among other Auger electron emitters by releasing approximately 37 Auger and Coster-Kronig electrons per decay, which is one of the highest numbers in its category. It has also a convenient half-life of 73 h, a stable daughter product, established production methods, and demonstrated high radiotoxicity.

Radiotracers for in situ infection imaging: Experimental considerations for in vitro microbial uptake of gallium-68-labeled siderophores.

In vitro screening of gallium-68(Ga)-siderophores in pathogens relevant to infections is valuable for determining species specificity, their effect on cell viability, and potential clinical applications. As the recognition and internalization of siderophores relies on the presence of receptor- and/or siderophore-binding proteins, the level of uptake can vary between species. Here, we report in vitro uptake validation in Escherichia coli with its native siderophore, enterobactin (ENT) ([Ga]Ga-ENT), considering different experimental factors.

Is there a role for [F]-FMISO PET to guide dose adaptive radiotherapy in head and neck cancer? A review of the literature.

Purpose: Hypoxia is a major cause of radioresistance in head and neck cancer (HNC), resulting in treatment failure and disease recurrence. F-fluoromisonidazole [F]FMISO PET has been proposed as a means of localising intratumoural hypoxia in HNC so that radiotherapy can be specifically escalated in hypoxic regions. This concept may not be deliverable in routine clinical practice, however, given that [F]FMISO PET is costly, time consuming and difficult to access.

[Ga]Ga-Schizokinen, a Potential Radiotracer for Selective Bacterial Infection Imaging.

Gallium-68-labeled siderophores as radiotracers have gained interest for the development of infection-specific imaging diagnostics. Here, we report radiolabeling, screening, and pharmacokinetics (PK) of gallium-68-labeled schizokinen ([Ga]Ga-SKN) as a new potential radiotracer for imaging bacterial infections. We radiolabeled SKN with ≥95% radiochemical purity.

Receptor-Targeted Peptide Conjugates Based on Diphosphines Enable Preparation of Tc and Re Theranostic Agents for Prostate Cancer.

Benchtop Mo/Tc and W/Re generators enable economical production of molecular theranostic Tc and Re radiopharmaceuticals, provided that simple, kit-based chemistry exists to radiolabel targeting vectors with these radionuclides. We have previously described a diphosphine platform that efficiently incorporates Tc into receptor-targeted peptides. Here, we report its application to label a prostate-specific membrane antigen (PSMA)-targeted peptide with Tc and Re for diagnostic imaging and systemic radiotherapy of prostate cancer.

Optimised production of technetium-94m for PET imaging by proton-irradiation of phosphomolybdic acid in cyclotron liquid target.

Natural-abundance phosphomolybdic acid (H(MoPO) ‧12HO, 0.181-0.552 g Mo/mL) solutions were irradiated with 12.

The British nuclear medicine research strategy - the framework.

The British Nuclear Medicine Society (BNMS) has developed a Research Strategy framework led by the Research Champions of the BNMS and overseen by the BNMS Research and Innovation Committee. The objectives of the Research Strategy are to improve translation of cutting-edge nuclear medicine research from bench to bedside, the implementation of state-of-the-art multimodality technologies and to enhance multicentre radionuclide research in the UK. It strives to involve patients and the public in radionuclide research and to contribute to and work with the multi-professional national and international organisations involved in research with an ultimate aim to improve nuclear medicine services, and patients' outcomes and care.

In vivo real-time positron emission particle tracking (PEPT) and single particle PET.

Positron emission particle tracking (PEPT) enables 3D localization and tracking of single positron-emitting radiolabelled particles with high spatiotemporal resolution. The translation of PEPT to the biomedical imaging field has been limited due to the lack of methods to radiolabel biocompatible particles with sufficient specific activity and protocols to isolate a single particle in the sub-micrometre size range, below the threshold for capillary embolization. Here we report two key developments: the synthesis and Ga-radiolabelling of homogeneous silica particles of 950 nm diameter with unprecedented specific activities (2.

Radiochemistry and In Vivo Imaging of [Ti]Ti-THP-PSMA.

Titanium-45 (Ti) is a radionuclide with excellent physical characteristics for use in positron emission tomography (PET) imaging, including a moderate half-life (3.08 h), decay by positron emission (85%), and a low mean positron energy of 0.439 MeV.

Combined Vorinostat and Chloroquine Inhibit Sodium-Iodide Symporter Endocytosis and Enhance Radionuclide Uptake In Vivo.

Purpose: Patients with aggressive thyroid cancer are frequently failed by the central therapy of ablative radioiodide (RAI) uptake, due to reduced plasma membrane (PM) localization of the sodium/iodide symporter (NIS). We aimed to understand how NIS is endocytosed away from the PM of human thyroid cancer cells, and whether this was druggable in vivo.

Experimental Design: Informed by analysis of endocytic gene expression in patients with aggressive thyroid cancer, we used mutagenesis, NanoBiT interaction assays, cell surface biotinylation assays, RAI uptake, and NanoBRET to understand the mechanisms of NIS endocytosis in transformed cell lines and patient-derived human primary thyroid cells.

In Vivo Trafficking of the Anticancer Drug Tris(8-Quinolinolato) Gallium (III) (KP46) by Gallium-68/67 PET/SPECT Imaging.

KP46 (tris(hydroxyquinolinato)gallium(III)) is an experimental, orally administered anticancer drug. Its absorption, delivery to tumours, and mode of action are poorly understood. We aimed to gain insight into these issues using gallium-67 and gallium-68 as radiotracers with SPECT and PET imaging in mice.

Ga-bisphosphonates for the imaging of extraosseous calcification by positron emission tomography.

Radiolabelled bisphosphonates (BPs) and [F]NaF (F-fluoride) are the two types of radiotracers available to image calcium mineral (e.g. bone), yet only [F]NaF has been widely explored for the non-invasive molecular imaging of extraosseous calcification (EC) using positron emission tomography (PET) imaging.

Radiometal-Labeled Photoactivatable Pt(IV) Anticancer Complex for Theranostic Phototherapy.

A novel photoactivatable Pt(IV) diazido anticancer agent, , bearing a pendant deferoxamine (DFO) siderophore for radiometal chelation, has been synthesized for the study of its behavior with radionuclide imaging. complexation of Fe(III) and Ga(III) ions yielded new heterobimetallic complexes that maintain the photoactivation properties and photocytotoxicity of the parent Pt complex in human cancer cell lines. Radiolabeled ( = 68 min, positron emitter) was readily prepared under mild conditions and was stable in the dark upon incubation with human serum.

Impact of an loss-of-function variant on the pancreatic distribution of zinc and manganese: laser ablation-ICP-MS and positron emission tomography studies in mice.

Introduction: Common variants in the gene, encoding the secretory granule zinc transporter ZnT8 (expressed largely in pancreatic islet alpha and beta cells), are associated with altered risk of type 2 diabetes. Unexpectedly, rare loss-of-function (LoF) variants in the gene, described in heterozygous individuals only, are protective against the disease, even though knockout of the homologous gene in mice leads to unchanged or impaired glucose tolerance. Here, we aimed to determine how one or two copies of the mutant R138X allele in the mouse gene impacts the homeostasis of zinc at a whole-body (using non-invasive Zn PET imaging to assess the acute dynamics of zinc handling) and tissue/cell level [using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to map the long-term distribution of zinc and manganese in the pancreas].

Versatile Diphosphine Chelators for Radiolabeling Peptides with Tc and Cu.

We have developed a diphosphine (DP) platform for radiolabeling peptides with Tc and Cu for molecular SPECT and PET imaging, respectively. Two diphosphines, 2,3-bis(diphenylphosphino)maleic anhydride (DP) and 2,3-bis(di--tolylphosphino)maleic anhydride (DP), were each reacted with a Prostate Specific Membrane Antigen-targeted dipeptide (PSMAt) to yield the bioconjugates DP-PSMAt and DP-PSMAt, as well as an integrin-targeted cyclic peptide, RGD, to yield the bioconjugates DP-RGD and DP-RGD. Each of these DP-PSMAt conjugates formed geometric /-[MO(DP-PSMAt)] (M = Tc, Tc, Re; X = Ph, Tol) complexes when reacted with [MO] motifs.

Probing Unexpected Reactivity in Radiometal Chemistry: Indium-111-Mediated Hydrolysis of Hybrid Cyclen-Hydroxypyridinone Ligands.

Chelators based on hydroxypyridinones have utility in incorporating radioactive metal ions into diagnostic and therapeutic agents used in nuclear medicine. Over the course of our hydroxypyridinone studies, we have prepared two novel chelators, consisting of a cyclen (1,4,7,10-tetraazacyclododecane) ring bearing two pendant hydroxypyridinone groups, appended via methylene acetamide motifs at either the 1,4-positions () or 1,7-positions () of the cyclen ring. In radiolabeling reactions of or with the γ-emitting radioisotope, [In]In, we have observed radiometal-mediated hydrolysis of a single amide group of either or .

An indium-111-labelled membrane-targeted peptide for cell tracking with radionuclide imaging.

Cell labelling agents that enable longitudinal tracking of administered cells will support the clinical development of cell-based therapies. Radionuclide imaging with gamma and positron-emitting radioisotopes can provide quantitative and longitudinal mapping of cells . To make this widely accessible and adaptable to a range of cell types, new, versatile and simple methods for directly radiolabelling cells are required.

Imaging zinc trafficking in vivo by positron emission tomography with zinc-62.

Non-invasive imaging techniques to dynamically map whole-body trafficking of essential metals in vivo in health and diseases are needed. Despite 62Zn having appropriate physical properties for positron emission tomography (PET) imaging (half-life, 9.3 h; positron emission, 8.

Targeting integrin αvβ6 with gallium-68 tris (hydroxypyridinone) based PET probes.

Expression of the cellular transmembrane receptor αvβ6 integrin is mostly restricted to malignant epithelial cells in a wide variety of carcinomas, including pancreatic and others derived from epithelial tissues. Thus, this protein is considered an attractive target for tumour imaging and therapy. Two different Ga hexadentate tris (3,4-hydroxypyridinone) (THP) chelators were produced in this study and coupled to the αvβ6 integrin-selective peptide (FRGDLAFp(NMe)K) NHS chemistry.

PSMA-targeted NIR probes for image-guided detection of prostate cancer.

Tumour-targeted near-infrared (NIR) optical imaging is an emerging tool for the detection of malignant tissues. This modality can be useful in both diagnosis and intraoperative visualisation, to help defining tumour margins and allow a more precise removal of all the cancerous mass during surgery. In this context, we have developed a series of NIR fluorescent probes that target the prostate-specific membrane antigen (PSMA), an established biomarker overexpressed in prostate cancer.

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.

Non-invasive radionuclide imaging of trace metal trafficking in health and disease: "PET metallomics".

Several specific metallic elements must be present in the human body to maintain health and function. Maintaining the correct quantity (from trace to bulk) and location at the cell and tissue level is essential. The study of the biological role of metals has become known as metallomics.