Opioid Receptors and Ligands: Targets for Cancer Imaging and Therapy

Lever, John R.

doi:10.4172/2161-0444.1000131

Cited by 4 publications

(2 citation statements)

References 76 publications

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“…Interestingly, the sites also mediate cardiovascular effects, pruritus, urinary retention, wound healing, and infection virulence [4][5][6]. Further, opioid receptors are implicated in cell death and survival [7,8], and are targets for molecular imaging of cancer [9]. Certain cancers differentially express the three main receptor types, μ, κ and δ, with respect to normal tissues.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis and evaluation of 111In labeled DOTA-conjugated tetrapeptides having high affinity and selectivity for mu opioid receptors

Lever

Fergason-Cantrell

Carmack

et al. 2019

Nuclear Medicine and Biology

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Introduction-Peripheral mu (μ) opioid receptors are implicated in pain, bowel dysfunction and the progression of certain cancers. In an effort to identify radioligands well suited for imaging these peripheral sites, we have prepared and evaluated four hydrophilic [ 111 In]-labeled, DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) conjugated μ tetrapeptides. Methods-Peptides were prepared by solid-phase techniques, using orthogonal strategies to achieve branching to DOTA, and then characterized by HPLC, mass spectroscopy and amino acid analysis. Scaffolds included novel peptide H-Dmt-D-Ala-Phe-Orn-NH 2 (DAPO), where Dmt = 2´, 6´-dimethyltyrosine, and known peptide H-Dmt-D-Arg-Phe-Lys-NH 2 ([Dmt 1 ]DALDA). Constructs had DOTA conjugation at the Orn 4 or Lys 4 side chains, or to the C-terminal through a hexanoic acid-lysine linker. Indium(III) complexation and [ 111 In]-radiolabeling were accomplished by standard methods. Protein binding and Log D 7.4 were determined. Binding and pharmacological profiles were obtained in vitro. Biodistribution and radiometabolite studies were conducted using male CD-1 mice. Results-All four indium(III)-DOTA conjugates derived from DAPO and [Dmt 1 ]DALDA showed good selectivity and subnanomolar affinity for μ opioid receptors. One radioligand, H-Dmt-D-Ala-Phe-Orn(δ-[ 111 In]DOTA)-NH 2 , showed 25% specific binding in vivo to μ sites in mouse gut. Notably, this was the least polar of the series, and also showed low sensitivity to modulation of binding by sodium ions. All radioligands showed high kidney uptake of radiometabolites.

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Section: Introductionmentioning

confidence: 99%

Design, synthesis and evaluation of 111In labeled DOTA-conjugated tetrapeptides having high affinity and selectivity for mu opioid receptors

Lever

Fergason-Cantrell

Carmack

et al. 2019

Nuclear Medicine and Biology

View full text Add to dashboard Cite

show abstract

“…The net effect is prevention of inhibition of protein synthesis, and thereby OGF promotes corneal cell proliferation and wound healing [42,43]. FK962 is one of the better-characterized small molecule neurogenic stimulators.…”

Section: Naltrexone (Nxt)mentioning

confidence: 99%