Synthesis and evaluation of C-11, F-18 and I-125 small molecule radioligands for detecting oxytocin receptors
Open accessAbstract
Compounds 1-4 were synthesized and investigated for selectivity and potency for the oxytocin receptor (OTR) to determine their viability as radioactive ligands. Binding assays determined 1-4 to have high binding affinity for both the human and rodent OTR and also have high selectivity for the human OTR over human vasopressin V1a receptors (V1aR). Inadequate selectivity for OTR over V1aR was found for rodent receptors in all four compounds. The radioactive (C-11, F-18, and I-125) derivatives of 1-4 were synthesized and investigated for use as autoradiography and positron emission tomography (PET) ligands. Receptor autoradiography performed with [(125)I]1 and [(125)I]2 on rodent brain slices provided the first small molecule radioligand images of the OTR and V1aR. Biodistribution studies determined [(125)I]1 and [(125)I]2 were adequate for in vivo peripheral investigations, but not for central investigations due to low uptake within the brain. A biodistribution study with [(18)F]3 suggested brain uptake occurred slowly over time. PET imaging studies with [(18)F]3 and [(11)C]4 using a rat model provided insufficient uptake in the brain over a 90 and 45 min scan times respectively to merit further investigations in non-human primates.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The authors' novel small-molecule OXTR antagonists failed to detect OXTR binding sites in vivo with PET.
“Unfortunately, these compounds have not been found useful for detecting OXTR binding sites in vivo using PET.”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [91]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00129-0 · Cited by 18,139 · see citing works
Partition coefficients and their uses
Leo, A., Hansch, C., & Elkins, D. R. (1971) · Chemical Reviews · doi:10.1021/cr60274a001 · Cited by 4,253 · see citing works
Medicinal chemical properties of successful central nervous system drugs
Pajouhesh, H., & Lenz, G. R. (2005) · NeuroRx · doi:10.1602/neurorx.2.4.541 · Cited by 1,566 · see citing works
Promoting social behavior with oxytocin in high-functioning autism spectrum disorders.
Andari, E., Duhamel, J.-R., Zalla, T., Herbrecht, E., Leboyer, M., & Sirigu, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910249107 · Cited by 941 · see citing works
Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles
Insel, T. R., & Shapiro, L. E. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.13.5981 · Cited by 833 · see citing works
Neuropeptidergic regulation of affiliative behavior and social bonding in animals
Lim, M. M., & Young, L. J. (2006) · Hormones and Behavior · doi:10.1016/j.yhbeh.2006.06.028 · Cited by 624 · see citing works
Self-citationWaterhouse, R. N. (2003) · Molecular Imaging and Biology · doi:10.1016/j.mibio.2003.09.014 · Cited by 568 · see citing works
Insel, T. R. (1992) · Psychoneuroendocrinology · doi:10.1016/0306-4530(92)90073-g · Cited by 487 · see citing works
The P-Glycoprotein Efflux Pump: How Does it Transport Drugs?
Sharom, F. J. (1997) · The Journal of Membrane Biology · doi:10.1007/s002329900305 · Cited by 462 · see citing works
Ross, H. E., Freeman, S. M., Spiegel, L. L., Ren, X., Terwilliger, E. F., & Young, L. J. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5039-08.2009 · Cited by 322 · see citing works
Self-citationBao, Q., Newport, D. F., Chen, M., Stout, D. B., & Chatziioannou, A. F. (2009) · Journal of Nuclear Medicine · doi:10.2967/jnumed.108.056374 · Cited by 306 · see citing works
MANNING, M., STOEV, S., CHINI, B., DURROUX, T., MOUILLAC, B., & GUILLON, G. (2008) · Progress in Brain Research · doi:10.1016/s0079-6123(08)00437-8 · Cited by 296 · see citing works
Olazábal, D. E., & Young, L. J. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.04.017 · Cited by 289 · see citing works
Self-citationAdenosine Receptor Signaling Modulates Permeability of the Blood–Brain Barrier
Carman, A. J., Mills, J. H., Krenz, A., Kim, D.-G., & Bynoe, M. S. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3337-11.2011 · Cited by 276 · see citing works
Olazábal, D. E., & Young, L. J. (2006) · Hormones and Behavior · doi:10.1016/j.yhbeh.2005.12.010 · Cited by 230 · see citing works
Self-citationInsel, T. R., Gelhard, R., & Shapiro, L. E. (1991) · Neuroscience · doi:10.1016/0306-4522(91)90321-e · Cited by 209 · see citing works
Lim, M. M., Murphy, A. Z., & Young, L. J. (2004) · Journal of Comparative Neurology · doi:10.1002/cne.10973 · Cited by 163 · see citing works
Self-citationStructural modifications of glycopeptide antibiotics
Malabarba, A., Nicas, T. I., & Thompson, R. C. (1997) · Medicinal Research Reviews · doi:10.1002/(sici)1098-1128(199701)17:1 · Cited by 140 · see citing works
Schorscher-Petcu, A., Dupré, A., & Tribollet, E. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.06.016 · Cited by 111 · see citing works
Blood-brain barrier disruption using mannitol: time course and electron microscopy studies
Cosolo, W., Martinello, P., Louis, W. J., & Christophidis, N. (1989) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1989.256.2.r443 · Cited by 102 · see citing works
Goodman, M. M., Kung, M., Kabalka, G. W., et al. (1994) · Journal of Medicinal Chemistry · doi:10.1021/jm00036a020 · Cited by 88 · see citing works
Self-citationOxytocin Receptor Distribution Reflects Social Organization in Monogamous and Polygamous Voles
SHAPIRO, L. E., & INSEL, T. R. (1992) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1992.tb34380.x · Cited by 84 · see citing works
A simple, rapid procedure for nucleophilic radiosynthesis of aliphatic [18F]trifluoromethyl groups
Riss, P. J., & Aigbirhio, F. I. (2011) · Chemical Communications · doi:10.1039/c1cc15342k · Cited by 83 · see citing works
Wilson, A. A., & Houle, S. (1999) · Journal of Labelled Compounds and Radiopharmaceuticals · doi:10.1002/(sici)1099-1344(19991230)42:13 · Cited by 72 · see citing works
Williams, P. D., Clineschmidt, B. V., Erb, J. M., Freidinger, R. M., Guidotti, M. T., Lis, E. V., Pawluczyk, J. M., Pettibone, D. J., & Reiss, D. R. (1995) · Journal of Medicinal Chemistry · doi:10.1021/jm00023a002 · Cited by 55 · see citing works
Altered hepatic vasopressin and alpha 1-adrenergic receptors after chronic endotoxin infusion
Roth, B. L., & Spitzer, J. A. (1987) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1987.252.5.e699 · Cited by 37 · see citing works
Are there oxytocin receptors in the primate brain?
TOLOCZKO, D. M., YOUNG, L., & INSEL, T. R. (1997) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1997.tb51953.x · Cited by 33 · see citing works
Self-citationA nonpeptide oxytocin receptor antagonist radioligand highly selective for human receptors
Lemaire, W., O’Brien, J. A., Burno, M., Chaudhary, A., Dean, D. C., Williams, P. D., Freidinger, R. M., Pettibone, D. J., & Williams, D. L. (2002) · European Journal of Pharmacology · doi:10.1016/s0014-2999(02)02048-4 · Cited by 22 · see citing works
Voll, R. J., McConathy, J., Waldrep, M. S., et al. (2005) · Applied Radiation and Isotopes · doi:10.1016/j.apradiso.2005.04.008 · Cited by 16 · see citing works
Self-citationNonpeptide oxytocin antagonists: Analogs of L-371,257 with improved potency
Williams, P. D., Bock, M. G., Evans, B., et al. (1999) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(99)00181-x · Cited by 16 · see citing works
Plisson, C., Stehouwer, J. S., Voll, R. J., et al. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm061303s · Cited by 16 · see citing works
Self-citationMcCarron, J. A., & Pike, V. W. (2003) · Journal of Labelled Compounds and Radiopharmaceuticals · doi:10.1002/jlcr.745 · Cited by 8 · see citing works
Development of the radiosynthesis of high-specific-activity 123I-NKJ64
Tavares, A., Jobson, N. K., Dewar, D., et al. (2011) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2010.11.011 · Cited by 2 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [24]Lim MM Murphy AZ Young LJ J. Comp. Neurol 2004 468 555 14689486
Cited by
Sorted by citations
Neuromodulation by Oxytocin and Vasopressin
Stoop, R. (2012) · Neuron · doi:10.1016/j.neuron.2012.09.025 · Cited by 506 · see citing works
MDMA enhances emotional empathy and prosocial behavior
Hysek, C. M., Schmid, Y., Simmler, L. D., Domes, G., Heinrichs, M., Eisenegger, C., Preller, K. H., Quednow, B. B., & Liechti, M. E. (2014) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nst161 · Cited by 356 · see citing works
Freeman, S. M., & Young, L. J. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12382 · Cited by 196 · see citing works
“We have also developed other novel, small-molecule, highly selective OXTR antagonists as tools for behavioural pharmacology in NHP, as well as for potential tracers for in vivo positron emission tomography (PET) neuroimaging (91,92).”
BackgroundSelf-citationMacDonald, K., & Feifel, D. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00035 · Cited by 181 · see citing works
Neurobiological mechanisms of social attachment and pair bonding
Johnson, Z. V., & Young, L. J. (2015) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2015.01.009 · Cited by 169 · see citing works
Self-citationSex, Receptors, and Attachment: A Review of Individual Factors Influencing Response to Oxytocin
MacDonald, K. S. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2012.00194 · Cited by 119 · see citing works
Oxytocin receptors modulate a social salience neural network in male prairie voles
Johnson, Z. V., Walum, H., Xiao, Y., Riefkohl, P. C., & Young, L. J. (2017) · Hormones and Behavior · doi:10.1016/j.yhbeh.2016.10.009 · Cited by 113 · see citing works
Self-citationIntranasal oxytocin effects on social cognition: A critique
Evans, S. L., Dal Monte, O., Noble, P., & Averbeck, B. B. (2014) · Brain Research · doi:10.1016/j.brainres.2013.11.008 · Cited by 97 · see citing works
Selective localization of oxytocin receptors and vasopressin 1a receptors in the human brainstem
Freeman, S. M., Smith, A. L., Goodman, M. M., & Bales, K. L. (2017) · Social Neuroscience · doi:10.1080/17470919.2016.1156570 · Cited by 51 · see citing works
Self-citationSmith, A. L., Freeman, S. M., Voll, R. J., Young, L. J., & Goodman, M. M. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2012.10.116 · Cited by 38 · see citing works
Self-citationOlazábal, D. E. (2014) · Journal of Physiology-Paris · doi:10.1016/j.jphysparis.2014.10.002 · Cited by 35 · see citing works
Investigation of an F-18 oxytocin receptor selective ligand via PET imaging
Smith, A. L., Freeman, S. M., Voll, R. J., Young, L. J., & Goodman, M. M. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.07.045 · Cited by 28 · see citing works
Self-citation
- Authors
- Smith, A. L., Freeman, S. M., Stehouwer, J. S., Inoue, K., Voll, R. J., Young, L. J., & Goodman, M. M.
- Affiliations
- Emory University (US)
- Emory National Primate Research Center (US)
- Corresponding author
- Young, Larry J.
- Goodman, Mark M.
- Venue
- Bioorganic & Medicinal Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 20
- Issue
- 8
- Pages
- 2721-2738
- ISSN
- 0968-0896 (ISSN-L)
- PMC
- PMC3701955
- OpenAlex
- W2051376655
- Cited by
- 35
- References
- 33
- Citations by year
- 2025: 1 · 2024: 1 · 2021: 1 · 2020: 4 · 2017: 3 · 2016: 10 · 2015: 1 · 2014: 6 · 2013: 7 · 2012: 1
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Bioorganic & Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (P51OD011132)
- National Institute of Mental Health (K02MH064692, MH064692, R21MH090776)
- National Center for Research Resources (RR-00 165, P51RR000165)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- oxytocin receptor, radioligands, vasopressin V1a receptor, receptor selectivity, autoradiography, positron emission tomography, tissue distribution, brain uptake
- MeSH terms
- Animals, Autoradiography, Binding, Competitive, Carbon Isotopes, Cell Line, Arvicolinae, Female, Fluorine Radioisotopes, Humans, Iodine Radioisotopes, Ligands, Molecular Weight, Piperidines, Quinolines, Radioligand Assay, Structure-Activity Relationship, Tissue Distribution, Molecular Structure, Rats, Sprague-Dawley, Receptors, Oxytocin, Radiopharmaceuticals, Positron-Emission Tomography, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
