First Example of a 99mTc Complex as a Dopamine Transporter Imaging Agent

Meegalla, Sanath K.; Plöessl, Karl; Kung, Mei‐Ping; Stevenson, D. Andrew; Liable‐Sands, Louise M.; Rheingold, Arnold L.; Kung, Hank F.

doi:10.1021/ja00149a039

Cited by 97 publications

(50 citation statements)

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“…While this system does not overcome the problem of stereoisomer formation, it is promising because of the straightforward functionalisation strategy via an ester group, the small size and the high lipophilicity of the complex. The rhenium complex is less polar than Tc(V)-oxo molecules and revealed a tenfold enhanced affinity towards monoamine transporters compared with native β-CFT or "3+1" complexes derived from IPT [52]. IC 50 values for the analogue are 7.3±1.1 nM for NET (β-CFT, 834±45 nM) and 71±1.4 nM for 5HTT (β-CFT, 759±47 nM).…”

Section: Examples Of Small Molecules Labelled With Tc/re-tricarbonylmentioning

confidence: 96%

Current use and future potential of organometallic radiopharmaceuticals

Schibli

Schubiger

2002

European Journal of Nuclear Medicine and Molecular Imaging

300

256

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Contrary to common belief, organometallic compounds exhibit remarkable stability in aerobic and even diluted aqueous solutions. Technetium-sestamibi (Cardiolite) is one of the most prominent examples of this class of compounds routinely used in nuclear medicine. This review summarises the recent progress in labelling of biomolecules with organometallic complexes for diagnostic and therapeutic application in radiopharmacy and exemplifies in detail developments focussing on organometallic technetium- and rhenium-tricarbonyl technologies. The value of such technologies has been recognised and they have become a valuable alternative to common labelling methodologies. An increasing number of groups have started to employ an organometallic precursor for the purpose of radioactive labelling of various classes of biomolecules, and the advantages and limitations of this new technique are compared with those of other labelling methods. The synthetic access to appropriate precursors via double-ligand exchange or aqueous carbonyl kit preparation for routine application is described. Strategies and examples for the design of appropriate bifunctional chelating agents for the Tc/Re-tricarbonyl core are given. The functionalization of biomolecules such as tracers for the central nervous system (dopaminergic and serotonergic), tumour affine peptides (somatostatin receptors, neuroreceptors) and tumour binding single-chain antibody fragments is summarised. Where possible and appropriate, the in vitro and in vivo results in respect of these examples are compared with those obtained with classical (99m)Tc/(188)Re(V)- and (111)In-labelled analogues. The preclinical results show the in many ways superior characteristics of organometallic labelling techniques.

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Section: Examples Of Small Molecules Labelled With Tc/re-tricarbonylmentioning

confidence: 96%

Current use and future potential of organometallic radiopharmaceuticals

Schibli

Schubiger

2002

European Journal of Nuclear Medicine and Molecular Imaging

300

256

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“…Several ligands have been reported for use in PET imaging, including [ 11 C]cocaine, 5 [ 11 C]-2b-carbomethoxy-3b-(4-iodophenyl)tropane ) or N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl)tropane (FPbCIT 7 ). Positron-emitting nuclides have short half-lives (e.g., 11 C, 20 min; 18 F, 109 min), so they require an on-site cyclotron for their production. More recently, SPECT Tc.…”

Section: Introductionmentioning

confidence: 99%

“…All the examples of Tc-99m labelled tropane derivatives have been modified at the N-position (R 1 ) or at C 2 (R 2 ) to introduce a technetium-carrying moiety. The best candidates are technepine, 10 ''3+1''-mixed-ligand 11 and TRODAT-1 12 which showed a good fixation on striatum neurons. Nevertheless, they are still not perfect for the development of a SPECT imaging agent of dopaminergic neuronal function.…”

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confidence: 99%

Synthesis of two novel oxocyclam‐binding technetium complexes containing an analogue of cocaine

Turpin¹,

Masri

Riche

et al. 2002

Labelled Comp Radiopharmac

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International audienceIn order to visualize and quantify dopamine transporters, the synthesis of two novel ligands labelled with technetium-99 m (99mTc) has been investigated. A multi-step synthesis afforded two target ligands with a tropane skeleton and a macrocyclic complexing moiety. The choice and the position of substituents are in adequation with dopamine transporter structure. The radiolabelling of these ligands with 99mTc has been studied and the results make them good candidates for SPECT imaging

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“…Recent studies aimed at the preparation of 123 Iand 99m Tc-labeled radiotracers for single photon emission computed tomography (SPECT) studies of DAT indicate that there is a large degree of bulk tolerance in the bridgehead nitrogen region of the cocaine-congeners with respect to DAT binding affinity Meegalla et al, 1995;Madras et al, 1996;Meltzer et al, 1997). These studies indicate that it should be possible to substitute the bridgehead nitrogen atom of N-methyl tropane analogs with an N-[ 18 F]4Ј-fluorobenzyl group without causing a dramatic reduction in affinity for DAT.…”

Section: Introductionmentioning

confidence: 99%