A comparative evaluation of calix[4]arene-1,3-crown-6 as a ligand for selected divalent cations of radiopharmaceutical interest

Bauer, David; Blumberg, Markus; Köckerling, Martin; Mamat, Constantin

doi:10.1039/c9ra07293d

Cited by 21 publications

(18 citation statements)

References 48 publications

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“…The major limitation of radium is the lack of an organic or inorganic framework to bind this radionuclide stably [ 11 ]. Despite several approaches to coordinate Ra 2+ , (e.g., using macrocyclic ligands [ 12 , 13 , 14 , 15 ], inorganic nanomatrices such as nanoparticles based on BaSO 4 [ 16 , 17 ], barium ferrite [ 18 ], TiO 2 and hydroxyapatite [ 19 , 20 ] or polyoxometalates [ 21 ]), an ideal carrier was not found, yet.…”

Section: Introductionmentioning

confidence: 99%

Towards Targeted Alpha Therapy with Actinium-225: Chelators for Mild Condition Radiolabeling and Targeting PSMA—A Proof of Concept Study

Reissig

Bauer

Zarschler

et al. 2021

Cancers

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Currently, targeted alpha therapy is one of the most investigated topics in radiopharmaceutical cancer management. Especially, the alpha emitter 225Ac has excellent nuclear properties and is gaining increasing popularity for the treatment of various tumor entities. We herein report on the synthesis of two universal 225Ac-chelators for mild condition radiolabeling and binding to conjugate molecules of pharmacological interest via the copper-mediated click chemistry. A convenient radiolabeling procedure was investigated as well as the complex stability proved for both chelators and two PSMA (prostate-specific membrane antigen)-targeting model radioconjugates. Studies regarding affinity and cell survival were performed on LNCaP cells followed by biodistribution studies, which were performed using LNCaP tumor-bearing mice. High efficiency radiolabeling for all conjugates was demonstrated. Cell binding studies revealed a fourfold lower cell affinity for the PSMA radioconjugate with one targeting motif compared to the radioconjugate owing two targeting motifs. Additionally, these differences were verified by in vitro cell survival evaluation and biodistribution studies, both showing a higher cell killing efficiency for the same dose, a higher tumor uptake (15%ID/g) and a rapid whole body clearance after 24 h. The synthesized chelators will overcome obstacles of lacking stability and worse labeling needs regarding 225Ac complexation using the DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid) chelator. Moreover, the universal functionalization expands the coverage of these chelators in combination with any sensitive bio(macro)molecule, thus improving treatment of any addressable tumor target.

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Section: Introductionmentioning

confidence: 99%

Towards Targeted Alpha Therapy with Actinium-225: Chelators for Mild Condition Radiolabeling and Targeting PSMA—A Proof of Concept Study

Reissig

Bauer

Zarschler

et al. 2021

Cancers

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“…Barium-131 has the potential to be stably bound within any appropriate vehicle system, analogously as recently reported for radium; current studies are investigating the possibilities of incorporating radium ions into nanoparticles [ 16 ], e.g., based on hydroxyapatite [ 17 , 18 ]. Additionally, some approaches deal with the chelation of radium ions by organic ligands based on the calix [ 4 ] arene scaffold [ 19 , 20 , 21 ]. The chelator macropa, which is already under investigation as suitable chelator for actinium-225, could be—as recently reported [ 22 , 23 , 24 ]—particularly promising for heavy alkaline earth metals like radium.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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 133Cs(p,3n)131Ba by using 27.5 MeV proton beams. An average of 190 MBq barium-131 per irradiation was obtained. The SR Resin-based purification process led to barium-131 in high radiochemical purity. An isotopic impurity of 0.01% barium-133 was detectable. For the first time, radiolabeling of the ligand macropa with barium-131 was performed. Radiolabeling methods under mild conditions and reaction controls based on TLC systems were successfully applied. Small animal SPECT/ computed tomography (CT) measurements and biodistribution studies were performed using [131Ba]Ba(NO3)2 as reference and 131Ba-labeled macropa in healthy mice for the first time. Biodistribution studies revealed the expected rapid bone uptake of [131Ba]Ba2+, whereas 131Ba-labeled macropa showed a fast clearance from the blood, thereby showing a significantly (p < 0.001) lower accumulation in the bone. We conclude that barium-131 is a promising SPECT radionuclide and delivers appropriate imaging qualities in small animals. Furthermore, the relative stability of the 131Ba-labeled macropa complex in vivo forms the basis for the development of sufficient new chelators, especially for radium isotopes. Thereby, barium-131 will attain its goal as a diagnostic match to the alpha emitters radium-223 and radium-224.

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“…However, robust and sufficiently stable carrier systems for barium and radium ions have not been reported so far by other groups. Macrocyclic chelators based on calixarenes for stable complexation of radium isotopes have been investigated in our group, [16] but respective ligands with adequate kinetic stability are yet to be discovered.…”

Section: Introductionmentioning

confidence: 99%

Sub‐10 nm Radiolabeled Barium Sulfate Nanoparticles as Carriers for Theranostic Applications and Targeted Alpha Therapy

et al. 2020

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The treatment of cancer patients with α‐particle‐emitting therapeutics continues to gain in importance and relevance. The range of radiopharmaceutically relevant α‐emitters is limited to a few radionuclides, as stable chelators or carrier systems for safe transport of the radioactive cargo are often lacking. Encapsulation of α‐emitters into solid inorganic systems can help to diversify the portfolio of candidate radionuclides, provided, that these nanomaterials effectively retain both the parent and the recoil daughters. We therefore focus on designing stable and defined nanocarrier‐based systems for various clinically relevant radionuclides, including the promising α‐emitting radionuclide 224Ra. Hence, sub‐10 nm barium sulfate nanocontainers were prepared and different radiometals like 89Zr, 111In, 131Ba, 177Lu or 224Ra were incorporated. Our system shows stabilities of >90 % regarding the radiometal release from the BaSO4 matrix. Furthermore, we confirm the presence of surface‐exposed amine functionalities as well as the formation of a biomolecular corona.

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A comparative evaluation of calix[4]arene-1,3-crown-6 as a ligand for selected divalent cations of radiopharmaceutical interest

Abstract: The stability constants of the promising ligand calix[4]arene-1,3-crown-6 and divalent metals of radiopharmaceutical interest: lead, barium, and strontium, were determined via NMR and UV/Vis techniques.

Cited by 21 publications

References 48 publications

Towards Targeted Alpha Therapy with Actinium-225: Chelators for Mild Condition Radiolabeling and Targeting PSMA—A Proof of Concept Study

Towards Targeted Alpha Therapy with Actinium-225: Chelators for Mild Condition Radiolabeling and Targeting PSMA—A Proof of Concept Study

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

Sub‐10 nm Radiolabeled Barium Sulfate Nanoparticles as Carriers for Theranostic Applications and Targeted Alpha Therapy

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