Chelation with a twist: a bifunctional chelator to enable room temperature radiolabeling and targeted PET imaging with scandium-44

Vaughn, Brett A.; Ahn, Shin Hye; Aluicio‐Sarduy, Eduardo; Devaraj, Justin; Olson, Aeli P.; Engle, Jonathan W.; Boros, Eszter

doi:10.1039/c9sc04655k

Cited by 34 publications

(84 citation statements)

References 53 publications

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“…4 ppm ( Supplementary Fig. 1), and the large 45 Sc chemical shift upon complexation indicates 343-HOPO effectively shields the 45 Sc nucleus from solvent molecules (vide infra) 13 . The single peak in the 45 Sc NMR spectrum for [Sc-343-HOPO] − also suggests no metal-centered isomerism on the NMR timescale, consistent with only a single species in solution.…”

Section: Resultsmentioning

confidence: 99%

“…However, this approach is hindered by the different ionic radii of these elements (CN = 6, 0.62 Å for Ga 3+ ; CN = 8, 0.977 Å for Lu 3+ ; CN = 8, 1.019 Å for Y 3+ ) 7,8 , which leads to mismatches in coordination chemistry and varying in vivo behavior [9][10][11] . The identification of chemically identical (i.e., isotopic) pairs of radionuclides with complementary nuclear properties is valuable for the development of new theranostic agents, and 44 Sc/ 47 Sc and 86 Y/ 90 Y are two pairs with great promise in this arena 1,[12][13][14] .…”

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confidence: 99%

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Developing scandium and yttrium coordination chemistry to advance theranostic radiopharmaceuticals

et al. 2020

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The octadentate siderophore analog 3,4,3-LI(1,2-HOPO), denoted 343-HOPO hereafter, is known to have high affinity for both trivalent and tetravalent lanthanide and actinide cations. Here we extend its coordination chemistry to the rare-earth cations Sc 3+ and Y 3+ and characterize fundamental metal-chelator binding interactions in solution via UV-Vis spectrophotometry, nuclear magnetic resonance spectroscopy, and spectrofluorimetric metalcompetition titrations, as well as in the solid-state via single crystal X-ray diffraction. Sc 3+ and Y 3+ binding with 343-HOPO is found to be robust, with both high thermodynamic stability and fast room temperature radiolabeling, indicating that 343-HOPO is likely a promising chelator for in vivo applications with both metals. As a proof of concept, we prepared a 86 Y-343-HOPO complex for in vivo PET imaging, and the results presented herein highlight the potential of 343-HOPO chelated trivalent metal cations for therapeutic and theranostic applications.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Developing scandium and yttrium coordination chemistry to advance theranostic radiopharmaceuticals

et al. 2020

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“…Sc(picaga)-DUPA exhibited a K i of 1.6 nM for PSMA and the 44 Sc labelled Sc(picaga)-DUPA revealed high-quality images in prostate cancer-bearing animals. H 3 mpatcn and its bifunctional analogue picaga represent new additions to the chelator toolbox for the emerging 44/47 Sc theragnostic isotope pair as reported by Vaughn et al (Vaughn et al 2020a). Nonetheless, the molar activity calculated from their experimental data was estimated to be 0.03 MBq/nmol and thus the metal to ligand ratio was ranging between 1: 485,500 to 1: 1,084,600.…”

Section: Chelators For Scmentioning

confidence: 97%

Production of scandium radionuclides for theranostic applications: towards standardization of quality requirements

Mikołajczak

Huclier‐Markai

Alliot

et al. 2021

EJNMMI radiopharm. chem.

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In the frame of “precision medicine”, the scandium radionuclides have recently received considerable interest, providing personalised adjustment of radiation characteristics to optimize the efficiency of medical care or therapeutic benefit for particular groups of patients. Radionuclides of scandium, namely scandium-43 and scandium-44 (43/44Sc) as positron emitters and scandium-47 (47Sc), beta-radiation emitter, seem to fit ideally into the concept of theranostic pair. This paper aims to review the work on scandium isotopes production, coordination chemistry, radiolabeling, preclinical studies and the very first clinical studies. Finally, standardized procedures for scandium-based radiopharmaceuticals have been proposed as a basis to pave the way for elaboration of the Ph.Eur. monographs for perspective scandium radionuclides.

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“…As discussed briefly in Section 4.2, 68 Ga is unlikely to be able to capture the full shape of the washout curve of 177 Lu and might not be suitable for late time-point imaging. The different coordination chemistry between 68 Ga and 177 Lu also results in differing lipophilicities, hydrophilicities, charge, receptor affinities and pharmacokinetics between labeled pharmaceuticals 67 , 163 - 165 .…”

Section: Examples Of Theranostic Pairsmentioning

confidence: 99%

Implications of physics, chemistry and biology for dosimetry calculations using theranostic pairs

Miller¹,

Rousseau²,

Ramogida³

et al. 2022

Theranostics

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Theranostics is an emerging paradigm that combines imaging and therapy in order to personalize patient treatment. In nuclear medicine, this is achieved by using radiopharmaceuticals that target identical molecular targets for both imaging (using emitted gamma rays) and radiopharmaceutical therapy (using emitted beta, alpha or Auger-electron particles) for the treatment of various diseases, such as cancer. If the therapeutic radiopharmaceutical cannot be imaged quantitatively, a “theranostic pair” imaging surrogate can be used to predict the absorbed radiation doses from the therapeutic radiopharmaceutical. However, theranostic dosimetry assumes that the pharmacokinetics and biodistributions of both radiopharmaceuticals in the pair are identical or very similar, an assumption that still requires further validation for many theranostic pairs. In this review, we consider both same-element and different-element theranostic pairs and attempt to determine if factors exist which may cause inaccurate dose extrapolations in theranostic dosimetry, either intrinsic (e.g. chemical differences) or extrinsic (e.g. injecting different amounts of each radiopharmaceutical) to the radiopharmaceuticals. We discuss the basis behind theranostic dosimetry and present common theranostic pairs and their therapeutic applications in oncology. We investigate general factors that could create alterations in the behavior of the radiopharmaceuticals or the quantitative accuracy of imaging them. Finally, we attempt to determine if there is evidence showing some specific pairs as suitable for theranostic dosimetry. We show that there are a variety of intrinsic and extrinsic factors which can significantly alter the behavior among pairs of radiopharmaceuticals, even if they belong to the same chemical element. More research is needed to determine the impact of these factors on theranostic dosimetry estimates and on patient outcomes, and how to correctly account for them.

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Chelation with a twist: a bifunctional chelator to enable room temperature radiolabeling and targeted PET imaging with scandium-44

Abstract: The small-cavity, bifunctional chelator picaga coordinates Sc-44 at room temperature and enables PET imaging of an in vivo tumor target.

Cited by 34 publications

References 53 publications

Developing scandium and yttrium coordination chemistry to advance theranostic radiopharmaceuticals

Developing scandium and yttrium coordination chemistry to advance theranostic radiopharmaceuticals

Production of scandium radionuclides for theranostic applications: towards standardization of quality requirements

Implications of physics, chemistry and biology for dosimetry calculations using theranostic pairs

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