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

Satpati, Drishty; Bapat, Ketaki; Sarma, Haladhar Dev; Kothari, Kanchan; Venkatesh, Meera; Banerjee, Sharmila

doi:10.1089/cbr.2007.763

Cited by 2 publications

(2 citation statements)

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“…Only moderate tumor-to-muscle ratios were reached at 24 h after injection in Swiss mice bearing fibrosarcoma tumors or C57BL6 mice bearing melanomas (2.0 and 3.5, respectively). Binding of the complex in the tumors appeared to be partially to sigma-1 receptors, since it was reduced by 40% after pretreatment of animals with 25 g of (+)-pentazocine [106].…”

Section: I]n-[2-(4-iodophenyl)ethyl]-nmethyl-2-(1-piperidinyl)ethylammentioning

confidence: 99%

Sigma Receptors in Oncology: Therapeutic and Diagnostic Applications of Sigma Ligands

Waarde¹,

Rybczynska²,

Ramakrishnan³

et al. 2010

CPD

100

105

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Sigma receptors (subtypes sigma-1 and sigma-2) are a unique class of binding sites expressed throughout the mammalian body. The endogenous ligand for these sites has not been identified, but steroid hormones (particularly progesterone), sphingolipid-derived amines and N,N-dimethyltryptamine can bind with fairly high affinity. Sigma receptors are overexpressed in rapidly proliferating cells, like cancer cells. Particularly the sigma-2 subtype is upregulate when cells divide and down regulated when they become quiescent. Sigma ligands, especially sigma-2 agonists, can inhibit proliferation and induce apoptosis by a mechanism involving changes in cytosolic Ca(2+), ceramide and sphingolipid levels. Tumor cells are much more sensitive to such treatment than cells from their tissue of origin. Sigma ligands induce apoptosis not only in drug-sensitive but also in drug-resistant cancer cells (e.g., cells with p53 mutations, or caspase dysfunction). Moreover, sigma ligands may abrogate P-glycoprotein-mediated drug resistance and at subtoxic doses, they can potentiate the effect of conventional cytostatics. Thus, sigma-2 agonists may be developed as antineoplastic agents for the treatment of drug-resistant tumors. A large number of radiolabeled sigma ligands has been prepared for SPECT (single-photon emission computed tomography) and PET (positron emission tomography) imaging. Such radiopharmaceuticals can be used for tumor detection, tumor staging, and evaluation of anti-tumor therapy. There is still a need for the development of ligands with (1) high selectivity for the sigma-2 subtype, (2) defined action (agonist or antagonist) and (3) optimal pharmacokinetics (low affinity for P-glycoprotein, high and specific tumor uptake, and rapid washout from non-target tissues).

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Section: I]n-[2-(4-iodophenyl)ethyl]-nmethyl-2-(1-piperidinyl)ethylammentioning

confidence: 99%

Sigma Receptors in Oncology: Therapeutic and Diagnostic Applications of Sigma Ligands

Waarde¹,

Rybczynska²,

Ramakrishnan³

et al. 2010

CPD

100

105

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“…21 core was prepared using the kit following a procedure reported earlier. 22 The complex was then prepared by incubation of L1 with the [ Tc-nitrido intermediate corresponding to 498% of activity moved with the solvent front (R f = 0.8-1.0) with reduced technetium remaining at the origin. Radiochemical purity of the complex (498%) could be determined by TLC in saline wherein the complex remained at the origin (R f = 0).…”

Section: Chemistrymentioning

confidence: 99%

Synthesis, characterization and biological activity of ^99mTc‐labeled piperidine analogues targeting sigma receptors

Satpati

Bapat

Sarma

et al. 2010

Labelled Comp Radiopharmac

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Sigma receptors are expressed in high density in various types of cancer cells including brain tumours and are also involved in various diseases of central nervous system. This makes ligands that bind to these receptors, attractive molecular vectors for targeting radiation to the specific sites with the purpose of imaging and therapy of neurological disorders. We report synthesis of three derivatives of 4‐amino‐N‐benzylpiperidine namely, 4‐dithiocarbamato‐N‐benzylpiperidine, 4‐iminodiacetato‐N‐benzylpiperidine and 4‐(N‐benzylpiperidine)‐pyridin‐2‐ylmethyl‐amino)‐acetic acid and their radiolabeling with technetium‐99m. The in vivo evaluation of these radiolabeled compounds has been carried out in mice, for assessment of their binding affinity with sigma receptors. Of the three complexes, [99mTcN]‐4‐dithiocarbamato‐N‐benzylpiperidine, [99mTcN]Pip‐DTC exhibited the most promising characteristics with brain uptake of 0.6% ID/g at 5 min.p.i. that reduced to 0.3% ID/g after 2 h.p.i. Competition experiment carried out with [99mTcN]Pip‐DTC complex, using (+)‐pentazocine showed its specificity towards sigma receptors, as was found to be evident from reduction in the brain uptake of this complex. Introduction of iminodiacetate and pyridine moieties and subsequent radiolabeling did not result in complexes with significant potential of targeting and binding with sigma receptors. Copyright © 2010 John Wiley & Sons, Ltd.

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

Cited by 2 publications

References 20 publications

Sigma Receptors in Oncology: Therapeutic and Diagnostic Applications of Sigma Ligands

Sigma Receptors in Oncology: Therapeutic and Diagnostic Applications of Sigma Ligands

Synthesis, characterization and biological activity of ^99mTc‐labeled piperidine analogues targeting sigma receptors

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

Cited by 2 publications

References 20 publications

Sigma Receptors in Oncology: Therapeutic and Diagnostic Applications of Sigma Ligands

Sigma Receptors in Oncology: Therapeutic and Diagnostic Applications of Sigma Ligands

Synthesis, characterization and biological activity of 99mTc‐labeled piperidine analogues targeting sigma receptors

Contact Info

Product

Resources

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

Synthesis, characterization and biological activity of ^99mTc‐labeled piperidine analogues targeting sigma receptors