Abstract
The use of fluorescent (or luminescent) and metal contrast agents in high-throughput screens, in vitro assays, and molecular imaging procedures has rapidly expanded in recent years. Here we describe the development and utility of high-affinity ligands for cancer theranostics and other in vitro screening studies. In this context, we also illustrate the syntheses and use of heteromultivalent ligands as targeted imaging agents.
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Abbreviations
- δ-OR:
-
Delta-opioid receptor
- Ado:
-
8-Amino-3,6-dioxaoctanoyl
- Arsenazo (III):
-
2,7-Bis(2-arsenophenylazo)-1,8-dihydroxyaphthalene-3,6-disulfonic acid
- BB:
-
Bromophenol blue
- Boc:
-
tert-Butyloxycarbonyl
- CCK(6):
-
Nle-Gly-Trp-Nle-Asp-Phe-NH2
- CCK(8):
-
Asp-Tyr-Nle-Gly-Trp-Nle-Asp-Phe-NH2
- CCK2R:
-
Cholecystokinin receptor subtype 2
- CDI:
-
N,N′-carbonyldiimidazole
- CEST:
-
Chemical exchange saturation transfer
- CH3CN:
-
Acetonitrile
- CT:
-
Computed tomography
- Cy5:
-
Cyanine 5 dye
- DCM:
-
Dichloromethane
- DELFIA:
-
Dissociation-enhanced lanthanide fluoroimmunoassay
- DIC:
-
N,N′-diisopropylcarbodiimide
- DIEA:
-
Diisopropylethylamine
- DMBA:
-
1,3-Dimethylbarbituric acid
- DMEM:
-
Dulbecco’s modified eagle medium
- DMF:
-
N,N′-dimethylformamide
- DMSO:
-
Dimethylsulfoxide
- Dmt:
-
2′,6′-Dimethyl-l-tyrosine
- DOTA:
-
1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid
- DPLCE:
-
c[dPen2,Cys5]enkephalin
- DTPA:
-
Diethylenetriamine-N,N,N′,N′,N²-pentaacetic acid
- EDC:
-
1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride
- EDT:
-
1,2-Ethanedithiol
- ESI-MS:
-
Electrospray ionization-mass spectrometry
- Fmoc:
-
(9H-fluoren-9-ylmethoxy)carbonyl
- FT-ICR:
-
Fourier transform-ion cyclotron resonance
- HBTU:
-
2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluoro-phosphate
- hMC4R:
-
Human melanocortin-4 receptor
- HOBt:
-
N-hydroxybenzotriazole
- HOCt:
-
6-Chloro-1H-hydroxybenzotriazole
- htBVLs:
-
Heterobivalent ligands
- htMVL:
-
Heteromultivalent ligand
- MALDI-TOF:
-
Matrix-assisted laser desorption ionization-time of flight
- MRI:
-
Magnetic resonance imaging
- MSH:
-
Melanocyte-stimulating hormone
- MSH-7:
-
Ser-Nle-Glu-His-dPhe-Arg-Trp
- Mtt:
-
4-Methyltrityl
- NDP-α-MSH:
-
Ac-Ser-Tyr-Ser-Nle-Glu-His-dPhe-Arg-Trp-Gly-Lys-Pro-Val-NH2
- NHS:
-
N-hydroxysuccinimide ester
- NIR:
-
Near-infrared
- PARACEST:
-
Paramagnetic chemical exchange saturation transfer
- Pbf:
-
2,2,4,6,7-Pentamethyl-dihydrobenzofuran-5-sulfonyl
- PEG:
-
Polyethyleneglycol
- Pego:
-
19-Amino-5-oxo-3,10,13,16-tetraoxa-6-azanonadecan-1-oic acid
- RP-HPLC:
-
Reverse-phase high-performance liquid chromatography
- SPECT:
-
Single photon emission computed tomography
- SPPS:
-
Solid-phase peptide synthesis
- TA:
-
Thioanisole
- tBu:
-
tert-butyl
- TFA:
-
Trifluoroacetic acid
- THF:
-
Tetrahydrofuran
- Tic:
-
1,2,3,4-Tetrahydroisoquinoline-3-carboxylic acid
- TIS:
-
Triisopropylsilane
- TRL:
-
Time-resolved luminescence
- Trt:
-
Triphenylmethyl (trityl)
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Acknowledgments
The authors would like to thank Prof. Robert J. Gillies and his team for development of various cell lines and animal model for δOR tumor animal model described in this work. This work was supported by the National Cancer Institute through NIH Grant R21CA133455-01, R01 CA09736, and R01 CA 123547, and by the U.S. Army Medical Research and Materiel Command under W81XWH-04-1-0731. This work was also supported by the Northeastern Ohio Animal Imaging Resource Center, an NIH-funded program, R24CA110943.
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Josan, J.S. et al. (2011). Fluorescent and Lanthanide Labeling for Ligand Screens, Assays, and Imaging. In: Satyanarayanajois, S. (eds) Drug Design and Discovery. Methods in Molecular Biology, vol 716. Humana Press. https://doi.org/10.1007/978-1-61779-012-6_6
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