Optimized methods for production and purification of Titanium-45

Chaple, Ivis F.; Thiele, Kathryn; Thaggard, Grace; Fernandez, Solana; Boros, Eszter; Lapi, Suzanne E.

doi:10.1016/j.apradiso.2020.109398

Cited by 21 publications

(30 citation statements)

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“…The hexadentate, tris‐hydroxamate chelator, desferrioxamine B (DFO), was previously shown to complex Ti 4+ , forming 1 : 1 species across a wide range of pH values [16] . DFO was successfully radiolabeled with 45 Ti, however labeling is only achieved at elevated pH (9–12) [14a] as DFO competes with a large excess of citrate present in the 45 Ti eluent following separation from the 45 Sc target. Citrate forms strong complexes with Ti 4+ , with [Ti(cit) 3 ] 8− dominating from pH 6–8.…”

Section: Resultsmentioning

confidence: 99%

“…[13] Oxalic acid [10c] and citric acid [10c] are of interest for the extraction and purification of radioactive Ti 4 + isotopes. [14] Ti 4 + exhibits parallels in reactivity and behavior to Fe 3 + . [9b, 15] This is likely due to comparable ionic radii (Fe 3 + = 0.645 Å, Ti 4 + = 0.605 Å) as well as the preference for 6-coordinate octahedral geometry.…”

Section: Introductionmentioning

confidence: 99%

“…The 45 Ti was prepared in the form of 45 TiCl 4 , and was found to have high liver and spleen uptake in vivo. [19] Additionally, Ascorbic acid complexes labeled with 14 C and 45 Ti were analyzed, however results indicated significant decomplexation occurred. In recent years, a novel solid-phase approach to form 45 Ti-(salan)(dipic) has been reported, which was utilized to probe the distribution of the corresponding Ti 4 + anticancer agent in vivo.…”

Section: Introductionmentioning

confidence: 99%

“…The radionuclide 45 Ti is a promising isotope for positron emission tomography (PET) imaging due to its high positron branching ratio (85 %), low emission of concurrent gamma (<1 %), and low average positron energy (439 keV), making its imaging quality comparable to the widely clinically used PET isotope 18 F ( t 1/2 =109.8 min, β + =96 %, E β+avg =250 keV) [14a, 18] . Additionally, 45 Ti has a half‐life of 3.08 hours, which is well matched with targeting vectors that exhibit short pharmacokinetic half‐lives.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, 45 Ti has a half‐life of 3.08 hours, which is well matched with targeting vectors that exhibit short pharmacokinetic half‐lives. The 45 Ti isotope is produced primarily via the proton bombardment of naturally monoisotopic scandium via the 45 Sc(p,n) 45 Ti reaction, accessible using standard, low energy biomedical cyclotrons (8–15 MeV) [14a, 18b] …”

Section: Introductionmentioning

confidence: 99%

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A General Design Strategy Enabling the Synthesis of Hydrolysis‐Resistant, Water‐Stable Titanium(IV) Complexes

et al. 2022

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Despite its prevalence in the environment, the chemistry of the Ti 4 + ion has long been relegated to organic solutions or hydrolyzed TiO 2 polymorphs. A knowledge gap in stabilizing molecular Ti 4 + species in aqueous environments has prevented the use of this ion for various applications such as radioimaging, design of water-compatible metal-organic frameworks (MOFs), and aqueous-phase catalysis applications. Herein, we show a thorough thermodynamic screening of bidentate chelators with Ti 4 + in aqueous solution, as well as computational and structural analyses of key compounds. In addition, the hexadentate analogues of catechol (benzene-1,2-diol) and deferiprone (3-hydroxy-1,2-dimethyl-4(1H)-pyridone), TREN-CAM and THP Me respectively, were assessed for chelation of the 45 Ti isotope (t 1/2 = 3.08 h, β + = 85 %, E β + = 439 keV) towards positron emission tomography (PET) imaging applications. Both were found to have excellent capacity for kit-formulation, and [ 45 Ti]Ti-TREN-CAM was found to have remarkable stability in vivo.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A General Design Strategy Enabling the Synthesis of Hydrolysis‐Resistant, Water‐Stable Titanium(IV) Complexes

et al. 2022

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Exploring the Potential of Nanogels: From Drug Carriers to Radiopharmaceutical Agents

Kubeil,

Suzuki,

Casulli

et al. 2023

Adv Healthcare Materials

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Nanogels open up access to a wide range of applications and offer among others hopeful approaches for use in the field of biomedicine. This review provides a brief overview of current developments of nanogels in general, particularly in the fields of drug delivery, therapeutic applications, tissue engineering and sensor systems. Specifically, cyclodextrin (CD)‐based nanogels are important because they have exceptional complexation properties and are highly biocompatible. Nanogels as a whole and CD‐based nanogels in particular can be customized in a wide range of sizes and equipped with a desired surface charge as well as containing additional molecules inside and outside, such as dyes, solubility‐mediating groups or even biological vector molecules for pharmaceutical targeting. Currently, biological investigations are mainly carried out in vitro, but more and more in vivo applications are gaining importance. Modern molecular imaging methods are increasingly being used for the latter. Due to an extremely high sensitivity and the possibility of obtaining quantitative data on pharmacokinetic and pharmacodynamic properties, nuclear methods such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) using radiolabeled compounds are particularly suitable here. The use of radiolabeled nanogels for imaging, but also for therapy, is being discussed.This article is protected by copyright. All rights reserved

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“Off‐Label Use” of the Siderophore Enterobactin Enables Targeted Imaging of Cancer with Radioactive Ti^(IV)

Koller,

Glaser,

DeLuca

et al. 2024

Angewandte Chemie

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The development of inert, biocompatible chelation methods is required to harness the emerging positron emitting radionuclide 45Ti for radiopharmaceutical applications. Herein, we evaluate the Ti(IV)‐coordination chemistry of four catechol‐based, hexacoordinate chelators using synthetic, structural, computational, and radiochemical approaches. The siderophore enterobactin (Ent) and its synthetic mimic TREN‐CAM, readily form mononuclear Ti(IV) species in aqueous solution at neutral pH. Radiolabeling studies revealed that Ent and TREN‐CAM form mononuclear complexes with the short‐lived, positron‐emitting radionuclide45Ti(IV), and that these complexes do not transchelate to plasma proteins in vitro and exhibit rapid renal clearance in naïve mice. These features guided efforts to target the 45Ti isotope to prostate cancer tissue through the design, synthesis, and evaluation of Ent‐DUPA, a small molecule conjugate composed of a prostate specific membrane antigen (PSMA) targeting peptide and a monofunctionalized Ent scaffold. The [45Ti][Ti(Ent‐DUPA)]2‐ complex formed readily at room temperature and in a tumor xenograft model in mice, displayed selective tumor tissue accumulation (8± 5%, n=5), and low off‐target uptake in other organs. Overall, this work demonstrates targeted imaging with 45Ti(IV), provides a foundation for advancing the application of 45Ti in nuclear medicine, and reveals that Ent can be repurposed as a 45Ti‐complexing cargo for targeted nuclear imaging applications.

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Optimized methods for production and purification of Titanium-45

Cited by 21 publications

References 20 publications

A General Design Strategy Enabling the Synthesis of Hydrolysis‐Resistant, Water‐Stable Titanium(IV) Complexes

A General Design Strategy Enabling the Synthesis of Hydrolysis‐Resistant, Water‐Stable Titanium(IV) Complexes

Exploring the Potential of Nanogels: From Drug Carriers to Radiopharmaceutical Agents

“Off‐Label Use” of the Siderophore Enterobactin Enables Targeted Imaging of Cancer with Radioactive Ti^(IV)

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Optimized methods for production and purification of Titanium-45

Cited by 21 publications

References 20 publications

A General Design Strategy Enabling the Synthesis of Hydrolysis‐Resistant, Water‐Stable Titanium(IV) Complexes

A General Design Strategy Enabling the Synthesis of Hydrolysis‐Resistant, Water‐Stable Titanium(IV) Complexes

Exploring the Potential of Nanogels: From Drug Carriers to Radiopharmaceutical Agents

“Off‐Label Use” of the Siderophore Enterobactin Enables Targeted Imaging of Cancer with Radioactive Ti(IV)

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“Off‐Label Use” of the Siderophore Enterobactin Enables Targeted Imaging of Cancer with Radioactive Ti^(IV)