Radioactive Metals in Imaging and Therapy

Rivas, Charlotte; Jackson, Jessica A.; Hungnes, Ingebjørg N; Michelle, T.

doi:10.1016/b978-0-08-102688-5.00010-6

Cited by 7 publications

(14 citation statements)

References 234 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Currently, 99m Tc imaging uses radiotracers that measure perfusion physiological processes. These 99m Tc-labeled radiopharmaceuticals are based on relatively simple, low molecular weight Tc complexes, and their physicochemical properties determine the biodistribution and disease-targeting capabilities . By contrast, radiopharmaceuticals that have more recently entered routine clinical use target receptors that are overexpressed in diseased tissue.…”

Section: Introductionmentioning

confidence: 99%

Diphosphine Bioconjugates via Pt(0)-Catalyzed Hydrophosphination. A Versatile Chelator Platform for Technetium-99m and Rhenium-188 Radiolabeling of Biomolecules

et al. 2023

Self Cite

View full text Add to dashboard Cite

The ability to append targeting biomolecules to chelators that efficiently coordinate to the diagnostic imaging radionuclide, 99m Tc, and the therapeutic radionuclide, 188 Re, can potentially enable receptor-targeted "theranostic" treatment of disease. Here we show that Pt(0)-catalyzed hydrophosphination reactions are well-suited to the derivatization of diphosphines with biomolecular moieties enabling the efficient synthesis of ligands of the type Ph 2 PCH 2 CH 2 P(CH 2 CH 2 −Glc) 2 (L, where Glc = a glucose moiety) using the readily accessible Ph 2 PCH 2 CH 2 PH 2 and acryl derivatives. It is shown that hydrophosphination of an acrylate derivative of a deprotected glucose can be carried out in aqueous media. Furthermore, the resulting glucose−chelator conjugates can be radiolabeled with either 99m Tc(V) or 188 Re(V) in high radiochemical yields (>95%), to furnish separable mixtures of cis-and trans-[M(O) 2 L 2 ] + (M = Tc, Re). Single photon emission computed tomography (SPECT) imaging and ex vivo biodistribution in healthy mice show that each isomer possesses favorable pharmacokinetic properties, with rapid clearance from blood circulation via a renal pathway. Both cis-[ 99m Tc(O) 2 L 2 ] + and trans-[ 99m Tc(O) 2 L 2 ] + exhibit high stability in serum. This new class of functionalized diphosphine chelators has the potential to provide access to receptor-targeted dual diagnostic/therapeutic pairs of radiopharmaceutical agents, for molecular 99m Tc SPECT imaging and 188 Re systemic radiotherapy.

show abstract

Section: Introductionmentioning

confidence: 99%

Diphosphine Bioconjugates via Pt(0)-Catalyzed Hydrophosphination. A Versatile Chelator Platform for Technetium-99m and Rhenium-188 Radiolabeling of Biomolecules

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…In recent years, macrocyclic derivatives of cyclen (1,4,7,10-tetraazacyclododecane, Chart ) and crown ethers, all bearing additional pendant coordinating groups, have demonstrated utility for complexing hard metal ions with expanded coordination spheres . In addition to providing complexes of high thermodynamic stability, the inclusion of the macrocyclic ring imparts high kinetic stability.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

Self Cite

View full text Add to dashboard Cite

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 (L 1 ) or 1,7-positions (L 2 ) of the cyclen ring. In radiolabeling reactions of L 1 or L 2 with the γ-emitting radioisotope, [111In]In3+, we have observed radiometal-mediated hydrolysis of a single amide group of either L 1 or L 2 . The reaction of either [111In]In3+ or [natIn]In3+ with either L 1 or L 2 , in aqueous alkaline solutions at 80 °C, initially results in formation of [In(L 1 )]+ or [In(L 2 )]+, respectively. Over time, each of these species undergoes In3+-mediated hydrolysis of a single amide group to yield species in which In3+ remains coordinated to the resultant chelator, which consists of a cyclen ring bearing a single hydroxypyridinone group and a single carboxylate group. The reactivity toward hydrolysis is higher for the L 1 complex compared to that for the L 2 complex. Density functional theory calculations corroborate these experimental findings and importantly indicate that the activation energy required for the hydrolysis of L 1 is significantly lower than that required for L 2 . This is the first reported example of a chelator undergoing radiometal-mediated hydrolysis to form a radiometalated complex. It is possible that metal-mediated amide bond cleavage is a source of instability in other radiotracers, particularly those in which radiometal complexation occurs in aqueous, basic solutions at high temperatures. This study highlights the importance of appropriate characterization of radiolabeled products.

show abstract

“…Technetium-99m ( 99m Tc: t 1/2 = 6.0 h; E γ = 140.5 keV, 89.1%) is the most used radionuclide in nuclear imaging procedures worldwide. 1,2 Despite recent concerns over production related shortages and the ever-increasing popularity of positron emission tomography (PET), ongoing development of single photon emission computed tomography (SPECT) technologies, particularly the development and implementation of cadmium–zinc–telluride (CZT) γ-detectors, and the potential of imaging specific molecular targets mean there is a continuing need to develop new 99m Tc radiopharmaceuticals. 3–6 The combination of 99m Tc and beta-emitting radioisotopes of rhenium ( 188 Re or 186 Re), using a single ligand to form essentially isostructural complexes, offers the possibility of a theranostic matched-pair.…”

Section: Introductionmentioning

confidence: 99%

Hexadentate technetium-99m bis(thiosemicarbazonato) complexes: synthesis, characterisation and biodistribution

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

Radioactive Metals in Imaging and Therapy

Cited by 7 publications

References 234 publications

Diphosphine Bioconjugates via Pt(0)-Catalyzed Hydrophosphination. A Versatile Chelator Platform for Technetium-99m and Rhenium-188 Radiolabeling of Biomolecules

Diphosphine Bioconjugates via Pt(0)-Catalyzed Hydrophosphination. A Versatile Chelator Platform for Technetium-99m and Rhenium-188 Radiolabeling of Biomolecules

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

Hexadentate technetium-99m bis(thiosemicarbazonato) complexes: synthesis, characterisation and biodistribution

Contact Info

Product

Resources

About