Radiometallation and photo-triggered release of ready-to-inject radiopharmaceuticals from the solid phase

Smilowicz, Dariusz; Eisenberg, Shawn; Ahn, Shin Hye; Koller, Angus J.; Lampkin, Philip P; Boros, Eszter

doi:10.1039/d2sc06977f

Cited by 4 publications

(2 citation statements)

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“… 154 To visualize liposome distribution and their accumulation sites, a 99m Tc-radiolabeled liposomal platform was employed by Silindir-Gunay et al for molecular tumour imaging SPECT and CT. 155 In principle, NCs such as liposomes can be labeled by indirect labeling that involves attaching a radiolabeled molecule (such as a chelator or a targeting ligand) to the surface of previously prepared NCs using conjugation chemistry 156 or by direct labeling via incorporating a radiolabeled ligand or chelator to label metal radionuclides into the NC's surface during the preparation. 157 The authors reported neutral and positive charged FA-conjugated and PEGylated DTPA-PE containing liposomes ( Fig. 11I ).…”

Section: Folic Acid (Fa)-conjugated Nanocarriersmentioning

confidence: 95%

Package delivered: folate receptor-mediated transporters in cancer therapy and diagnosis

Ahmadi,

Ritter,

von Woedtke

et al. 2024

Chem. Sci.

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Section: Folic Acid (Fa)-conjugated Nanocarriersmentioning

confidence: 95%

Package delivered: folate receptor-mediated transporters in cancer therapy and diagnosis

Ahmadi,

Ritter,

von Woedtke

et al. 2024

Chem. Sci.

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“…83 Our group addressed this problem by using traceless photocleavage of a fully assembled radiopharmaceutical from a water-compatible solid support (Figure 5). 84 A photoreactive, unnatural amino acid, 3-amino-3-(2-nitrophenyl)propionic acid (ANP), was introduced between the resin and the chelatepeptide construct. This approach is well established for the ablation and subsequent analysis of resin-appended peptides using matrix-assisted laser desorption/ionization (MALDI) but is also compatible with UV (365 nm) irradiation for release from the resin in an aqueous suspension.…”

Section: Radiosynthesis On a Solid Support: Photolysismentioning

confidence: 99%

Exploring Aqueous Coordination Chemistry of Highly Lewis Acidic Metals with Emerging Isotopes for Nuclear Medicine

Whetter,

Śmiłowicz,

Boros

2024

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: Nuclear medicine harnesses radioisotopes for the diagnosis and treatment of disease. While the isotopes 99m Tc and 111 In have enabled the clinical diagnosis of millions of patients over the past 3 decades, more recent clinical translation of numerous 68 Ga/ 177 Lu-based radiopharmaceuticals for diagnostic imaging and therapy underscores the clinical utility of metal-based radiopharmaceuticals in mainstream cancer treatment. In addition to such established radionuclides, advancements in radioisotope production have enabled the production of radionuclides with a broad range of half-lives and emission properties of interest for nuclear medicine. Chemical means to form kinetically inert, in vivo-compatible species that can be modified with disease-targeting vectors is imperative. This presents a challenge for radiosiotopes of elements where the aqueous chemistry is still underdeveloped and poorly understood. Here, we discuss our efforts to date in exploring the aqueous, radioactive coordination chemistry of highly Lewis acidic metal ions and how our discoveries apply to the diagnosis and treatment of cancer in preclinical models of disease. The scope of this Account includes approaches to aqueous coordination of to-date understudied highly Lewis acidic metal ions with radioisotopes of emerging interest and the modulation of well-understood coordination environments of radio-coordination complexes to induce metal-catalyzed reactivity for separation and pro-drug applications. First, we discuss the development of seven-coordinate, small-cavity macrocyclic chelator platform mpatcn/picaga as an exemplary case study, which forms robust complexes with 44 Sc/ 47 Sc isotopes. Due to the high chemical hardness and pronounced Lewis acidity of the Sc 3+ ion, the displacement of ternary ligand H 2 O by 18/nat F − can be achieved to form an inert Sc− 18/nat F bond. Corresponding coordination complex nat Sc− 18 F is in vivo compatible and forms a theranostic tetrad with corresponding 44 Sc/ 47 Sc, 177 Lu complexes all exhibiting homologous biodistribution profiles. Another exceptionally hard, highly Lewis acidic ion with underdeveloped aqueous chemistry and emerging interest in nuclear medicine is 45 Ti 4+ . To develop de novo approaches to the mononuclear chelation of this ion under aqueous conditions, we employed a fragment-based bidentate ligand screening approach which identified two leads. The screen successfully predicted the formation of [ 45 Ti][Ti(TREN-CAM)], a Ti-triscatechol complex that exhibits remarkable in vivo stability. Furthermore, the fragment-based screen also identified approaches that enabled solid-phase separation of Ti 4+ and Sc 3+ of interest in streamlining the isotope production of 45 Ti and accessing new ways to separate 44 Ti/ 44 Sc for the development of a longlived generator system. In addition to establishing the inert chelation of Ti 4+ and Sc 3+ , we introduce controlled, metal-induced reactivity of corresponding coordination complexes on macrosc...

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Red/near-infrared light triggered photorelease via sensitized photolysis

Lu,

Yang,

et al. 2024

Coordination Chemistry Reviews

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Radiometallation and photo-triggered release of ready-to-inject radiopharmaceuticals from the solid phase

Abstract: The efficient, large-scale synthesis of radiometallated radiopharmaceuticals represents an emerging clinical need which, to date, is inherently limited by time consuming, sequential procedures to conduct isotope separation, radiochemical labeling and...

Cited by 4 publications

References 62 publications

Package delivered: folate receptor-mediated transporters in cancer therapy and diagnosis

Package delivered: folate receptor-mediated transporters in cancer therapy and diagnosis

Exploring Aqueous Coordination Chemistry of Highly Lewis Acidic Metals with Emerging Isotopes for Nuclear Medicine

Red/near-infrared light triggered photorelease via sensitized photolysis

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