Technetium-99m nitrido radiopharmaceuticals with unprecedented biological properties

Duatti, Adriano; Boschi, Alessandra; Uccelli, Licia

doi:10.1590/s1516-89132002000500019

Cited by 12 publications

(4 citation statements)

References 4 publications

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“…The intermediate compound bearing the [Tc ≡N] 2+ core is then mixed with the sodium salt of N-ethoxy, N-ethyl dithiocarbamate, and β-methyl-cyclodextrin, which serves as a solubilizing agent, to obtain a neutral [ 99m Tc][TcN(NOEt) 2 ] compound. Radiochemical purity is checked by thin-layer chromatography [32]. Its unique imaging properties are remarkable and, for this reason, it underwent extensive clinical evaluation in patients.…”

Section: Technetium-99m Teboroximementioning

confidence: 99%

Technetium-99m Radiopharmaceuticals for Ideal Myocardial Perfusion Imaging: Lost and Found Opportunities

et al. 2022

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The favorable nuclear properties in combination with the rich coordination chemistry make technetium-99m the radioisotope of choice for the development of myocardial perfusion tracers. In the early 1980s, [99mTc]Tc-Sestamibi, [99mTc]Tc-Tetrofosmin, and [99mTc]Tc-Teboroxime were approved as commercial radiopharmaceuticals for myocardial perfusion imaging in nuclear cardiology. Despite its peculiar properties, the clinical use of [99mTc]Tc-Teboroxime was quickly abandoned due to its rapid myocardial washout. Despite their widespread clinical applications, both [99mTc]Tc-Sestamibi and [99mTc]Tc-Tetrofosmin do not meet the requirements of an ideal perfusion imaging agent due to their relatively low first-pass extraction fraction and high liver absorption. An ideal radiotracer for myocardial perfusion imaging should have a high myocardial uptake; a high and stable target-to-background ratio with low uptake in the lungs, liver, stomach during the image acquisition period; a high first-pass myocardial extraction fraction and very rapid blood clearance; and a linear relationship between radiotracer myocardial uptake and coronary blood flow. Although it is difficult to reconcile all these properties in a single tracer, scientific research in the field has always channeled its efforts in the development of molecules that are able to meet the characteristics of ideality as much as possible. This short review summarizes the developments in 99mTc myocardial perfusion tracers, which are able to fulfill hitherto unmet medical needs and serve a large population of patients with heart disease, and underlines their strengths and weaknesses, the lost and found opportunities thanks to the developments of the new ultrafast SPECT technologies.

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Section: Technetium-99m Teboroximementioning

confidence: 99%

Technetium-99m Radiopharmaceuticals for Ideal Myocardial Perfusion Imaging: Lost and Found Opportunities

et al. 2022

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“…4,7,8 Such fac -[ 99m Tc(CO) 3 L] n agents are more robust and have better pharmacokinetic properties than agents with bidentate ligands. 11 The γ -emitting 99m Tc radionuclide has ideal nuclear properties 12,13 for diagnostic applications in nuclear medicine. 1,14-17 …”

Section: Introductionmentioning

confidence: 99%

Complexes Possessing Rare “Tertiary” Sulfonamide Nitrogen-to-Metal Bonds of Normal Length: fac-[Re(CO)₃(N(SO₂R)dien)]PF₆ Complexes with Hydrophilic Sulfonamide Ligands

et al. 2014

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Tertiary sulfonamide nitrogen-to-metal bonds of normal length are very rare. We recently discovered such a bond in one class of fac-[Re(CO)3(N(SO2R)(CH2Z)2)]n complexes (Z = 2-pyridyl) with N(SO2R)dpa ligands derived from di-(2-picolyl)amine (N(H)dpa). fac-[M(CO)3(N(SO2R)(CH2Z)2)]n agents (M = 186/188Re, 99mTc) could find use as radiopharmaceutical bioconjugates when R is a targeting moiety. However, the planar, electron-withdrawing 2-pyridyl groups of N(SO2R)dpa destabilize the ligand to base and create relatively rigid chelate rings, raising the possibility that the rare M– N(sulfonamide) bond is an artifact of a restricted geometry. Also, the hydrophobic 2-pyridyl groups could cause undesirable accumulation in the liver, limiting future use in radiopharmaceuticals. Our goal is to identify a robust, hydrophilic, and flexible N(CH2Z)2 chelate framework. New C2-symmetric ligands, N(SO2R)(CH2Z)2 with (Z = CH2NH2; R = Me, dmb, or tol), were prepared by treating N(H)dien(Boc)2, a protected diethylenetriamine (N(H)dien) derivative, with methanesulfonyl chloride (MeSO2Cl), 3,5-dimethylbenzenesulfonyl chloride (dmbSO2Cl), and 4-methylbenzenesulfonyl chloride (tolSO2Cl). Treatment of fac-[Re(CO)3(H2O)3]+ with these ligands, designated as N(SO2R)dien, afforded new fac-[Re(CO)3(N(SO2R)dien)]PF6 complexes. Comparing the fac-[Re(CO)3(N(SO2Me)dien)]PF6 and fac-[Re(CO)3(N(SO2Me)dpa)]PF6 complexes, we find that the ReI–N(sulfonamide) bonds are normal in length and statistically identical and that the methyl 13C NMR signal has an unusually upfield shift compared to that in the free ligand. We attribute this unusual upfield shift to the fact that the sulfonamide N undergoes an sp2-to-sp3 rehybridization upon coordination to ReI in both complexes. Thus, the sulfonamide N of N(SO2R)dien ligands is a good donor, even though the chelate rings are conformationally flexible. Addition of the strongly basic and potentially monodentate ligand, 4-dimethylaminopyridine, did not affect the fac-[Re(CO)3(N(SO2tol)dien)]PF6 complex, even after several weeks. This complex is also stable to heat in aqueous solution. These results indicate that N(SO2R)dien ligands form fac-[Re(CO)3(N(SO2R)dien)]PF6 complexes sufficiently robust to be utilized for radiopharmaceutical development.

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“…In order to design a complex with a single unit of biologic substrate satisfying the tetravalency of the nitrido core, the two bidentate ligands should be different, one being a chelating group of the bioactive molecule and the other one being a heterodiphosphine of the type (i.e., POP, PSP, and PNP) acting as a coligand and leading to the formation of asymmetric complexes of the type [ 99m TcN(DTC)PXP] ϩ where X ϭ N, S, O. 22 Hence, the metal synthon [ 99m TcN(PNP)] 2ϩ can be used for the preparation of a wide range of complexes of varying lipophilicities by changing the heteroatom and length of the diphosphine bridge.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of ^99mTc-Nitrido Heterocomplex of Piperidine and In Vitro and In Vivo Evaluation of Its Affinity for Sigma Receptors

Satpati

Bapat²,

Sarma³

et al. 2008

Cancer Biotherapy and Radiopharmaceuticals

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Sigma receptors are overexpressed in various types of cancer cells, making ligands that bind to these receptors attractive vectors for targeting radiation to specific sites for the imaging and therapy of oncologic disorders. In this paper, we report the synthesis of a dithiocarbamate derivative of 4-amino-N-benzylpiperidine and its radiolabeling with the [(99m)TcN(PNP)](2+) metal synthon. The radiolabeled tracer has been evaluated for sigma-receptor specificity. The radiochemical purity of the (99m)Tc-complex was >98%. The in vitro cell-binding and competition studies of the complex showed affinity and specificity toward fibrosarcoma and melanoma cells. In vivo studies carried out in mice bearing melanoma and fibrosarcoma tumors showed tumor uptakes of 1% and 1.9%, respectively, at 3 hours postinjection. In vivo blocking studies were carried out, using (+)-pentazocine, a sigma-receptor-specific agent where approximately 40% decrease in the tumor uptake was observed. The affinity of [(99m)TcN(PNP)Pip-DTC](+) complex for sigma-receptor sites ascertained through in vitro and in vivo studies makes it a potential agent for further investigation.

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Technetium-99m nitrido radiopharmaceuticals with unprecedented biological properties

Cited by 12 publications

References 4 publications

Technetium-99m Radiopharmaceuticals for Ideal Myocardial Perfusion Imaging: Lost and Found Opportunities

Technetium-99m Radiopharmaceuticals for Ideal Myocardial Perfusion Imaging: Lost and Found Opportunities

Complexes Possessing Rare “Tertiary” Sulfonamide Nitrogen-to-Metal Bonds of Normal Length: fac-[Re(CO)₃(N(SO₂R)dien)]PF₆ Complexes with Hydrophilic Sulfonamide Ligands

Synthesis of ^99mTc-Nitrido Heterocomplex of Piperidine and In Vitro and In Vivo Evaluation of Its Affinity for Sigma Receptors

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Technetium-99m nitrido radiopharmaceuticals with unprecedented biological properties

Cited by 12 publications

References 4 publications

Technetium-99m Radiopharmaceuticals for Ideal Myocardial Perfusion Imaging: Lost and Found Opportunities

Technetium-99m Radiopharmaceuticals for Ideal Myocardial Perfusion Imaging: Lost and Found Opportunities

Complexes Possessing Rare “Tertiary” Sulfonamide Nitrogen-to-Metal Bonds of Normal Length: fac-[Re(CO)3(N(SO2R)dien)]PF6 Complexes with Hydrophilic Sulfonamide Ligands

Synthesis of 99mTc-Nitrido Heterocomplex of Piperidine and In Vitro and In Vivo Evaluation of Its Affinity for Sigma Receptors

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Complexes Possessing Rare “Tertiary” Sulfonamide Nitrogen-to-Metal Bonds of Normal Length: fac-[Re(CO)₃(N(SO₂R)dien)]PF₆ Complexes with Hydrophilic Sulfonamide Ligands

Synthesis of ^99mTc-Nitrido Heterocomplex of Piperidine and In Vitro and In Vivo Evaluation of Its Affinity for Sigma Receptors