Carbon-11 N-methyl alkylation of L-368,899 and in vivo PET imaging investigations for neural oxytocin receptors
Open accessAbstract
Compound L-368,899 was successfully alkylated with [(11)C]iodomethane to generate the oxytocin receptor selective (2R)-2-amino-N-((2S)-7,7-dimethyl-1-(((4-(o-tolyl)piperazin-1-yl)sulfonyl)methyl)bicyclo[2.2.1]heptan-2-yl)-N-[(11)C]methyl-3-(methylsulfonyl)propanamide ([(11)C]1) with very high radiochemical purity and high specific activity. PET imaging studies were performed with [(11)C]1 to investigate brain penetration and oxytocin receptor uptake using rat and cynomolgus monkey models. For rat baseline scans, brain penetration was observed with [(11)C]1, but no specific uptake could be distinguished in the brain region. By administering a peptide oxytocin receptor selective antagonist for peripheral blocking of oxytocin receptors, the uptake of [(11)C]1 was amplified in the rat brain temporarily to enable some visual uptake within the rat brain. A baseline scan of [(11)C]1 in a cynomolgus monkey model resulted in no detectable specific uptake in anticipated regions, but activity did accumulate in the choroid plexus.
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?
L-368,899 appears to accumulate in ventricles rather than neural tissue.
“However, after radiolabelling L-368,899 and performing in vivo PET imaging in macaques, we found that there is minimal uptake in the brain, and the compound appears to accumulate in the ventricles and not in neural tissue (100).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [100]
PET imaging after radiolabelling L-368,899 in macaques showed minimal brain uptake.
“However, after radiolabelling L-368,899 and performing in vivo PET imaging in macaques, we found that there is minimal uptake in the brain, and the compound appears to accumulate in the ventricles and not in neural tissue (100).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [100]
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
Oxytocin, vasopressin, and the neurogenetics of sociality
Donaldson, Z. R., & Young, L. J. (2008) · Science · doi:10.1126/science.1158668 · Cited by 1,645 · see citing works
Self-citationOxytocin in the Medial Amygdala is Essential for Social Recognition in the Mouse
Ferguson, J. N., Aldag, J. M., Insel, T. R., & Young, L. J. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-20-08278.2001 · Cited by 1,043 · see citing works
Self-citationIntranasal oxytocin improves emotion recognition for youth with autism spectrum disorders.
Guastella, A. J., Einfeld, S. L., Gray, K. M., Rinehart, N. J., Tonge, B. J., Lambert, T. J., & Hickie, I. B. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.020 · Cited by 962 · 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 and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior
Ross, H. E., & Young, L. J. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.05.004 · Cited by 856 · see citing works
Self-citationPlasma oxytocin levels in autistic children
Modahl, C., Green, L. A., Fein, D., Morris, M., Waterhouse, L., Feinstein, C., & Levin, H. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(97)00439-3 · Cited by 728 · see citing works
Genomic and epigenetic evidence for oxytocin receptor deficiency in autism
Gregory, S. G., Connelly, J. J., Towers, A. J., Johnson, J., Biscocho, D., Markunas, C. A., Lintas, C., Abramson, R. K., Wright, H. H., Ellis, P., et al. (2009) · BMC Medicine · doi:10.1186/1741-7015-7-62 · Cited by 576 · see citing works
Positive Association of the Oxytocin Receptor Gene (OXTR) with Autism in the Chinese Han Population
Wu, S., Jia, M., Ruan, Y., Liu, J., Guo, Y., Mei, S., Gong, X., Zhang, Y., Yang, X., & Zhang, D. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.03.013 · Cited by 553 · see citing works
Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism
Jacob, S., Brune, C. W., Carter, C. S., Leventhal, B. L., Lord, C., & Cook, E. H. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2007.02.001 · Cited by 425 · see citing works
Graustella, A. J., & MacLeod, C. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2012.01.002 · Cited by 379 · see citing works
Lerer, E., Levi, S., Salomon, S., Darvasi, A., Yirmiya, N., & Ebstein, R. P. (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002087 · Cited by 349 · see citing works
Mesotocin and nonapeptide receptors promote estrildid flocking behavior
Goodson, J. L., Schrock, S. E., Klatt, J. D., Kabelik, D., & Kingsbury, M. A. (2009) · Science · doi:10.1126/science.1174929 · Cited by 241 · see citing works
Tribollet, E., Charpak, S., Schmidt, A., Dubois-Dauphin, M., & Dreifuss, J. (1989) · The Journal of Neuroscience · doi:10.1523/jneurosci.09-05-01764.1989 · Cited by 228 · see citing works
Smith, A. S., Ågmo, A., Birnie, A. K., & French, J. A. (2010) · Hormones and Behavior · doi:10.1016/j.yhbeh.2009.12.004 · Cited by 228 · see citing works
Self-citationThe oxytocin system in drug discovery for autism: Animal models and novel therapeutic strategies
Modi, M. E., & Young, L. J. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.12.010 · Cited by 218 · see citing works
Self-citationBoccia, M. L., Goursaud, A.-P. S., Bachevalier, J., Anderson, K. D., & Pedersen, C. A. (2007) · Hormones and Behavior · doi:10.1016/j.yhbeh.2007.05.009 · Cited by 136 · see citing works
Kreisl, W. C., Liow, J., Kimura, N., Seneca, N. M., Zoghbi, S. S., Morse, C. L., Herscovitch, P., Pike, V. W., & Innis, R. B. (2010) · Journal of Nuclear Medicine · doi:10.2967/jnumed.109.070151 · Cited by 131 · 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
Williams, P. D., Anderson, P., Ball, R. G., Bock, M. G., Carroll, L., Chiu, S.-H. L., Clineschmidt, B. V., Culberson, J. C., & Erb, J. M. (1994) · Journal of Medicinal Chemistry · doi:10.1021/jm00031a004 · Cited by 90 · see citing works
Editorial comment: Oxytocin, vasopressin and social behavior
Young, L. J., & Flanagan-Cato, L. M. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2012.02.019 · Cited by 81 · see citing works
Self-citationWilson, 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
Eyal, S., Ke, B., Muzi, M., Link, J. M., Mankoff, D. A., Collier, A. C., & Unadkat, J. D. (2010) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2010.11 · Cited by 65 · see citing works
Guastella, A. J., & MacLeod, C. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2012.04.008 · Cited by 53 · see citing works
L-368,899, a potent orally active oxytocin antagonist for potential use in preterm labor
Pettibone, D. J., Clineschmidt, B. V., Guidotti, M. T., Lis, E. V., Reiss, D. R., Woyden, C. J., Bock, M. G., Evans, B. E., Freidinger, R. M., Hobbs, D. W., et al. (1993) · Drug Development Research · doi:10.1002/ddr.430300305 · Cited by 43 · see citing works
Bauer, M., Karch, R., Neumann, F., Wagner, C. C., Kletter, K., Müller, M., Löscher, W., Zeitlinger, M. A., & Langer, O. (2009) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2009.265 · Cited by 35 · see citing works
Smith, A. L., Freeman, S. M., Stehouwer, J. S., Inoue, K., Voll, R. J., Young, L. J., & Goodman, M. M. (2012) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2012.02.019 · Cited by 35 · see citing works
Self-citationAre 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-citation
Flagged first, then by citations
Research works printed but not linked: 1
- [19]Wilson AA Houle S Journal of Labelled Compounds & Radiopharmaceuticals 1999 42 1277
Cited by
Sorted by citations
Baribeau, D. A., & Anagnostou, E. A. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00335 · Cited by 229 · see citing works
Freeman, S. M., & Young, L. J. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12382 · Cited by 196 · see citing works
“However, after radiolabelling L-368,899 and performing in vivo PET imaging in macaques, we found that there is minimal uptake in the brain, and the compound appears to accumulate in the ventricles and not in neural tissue (100).”
BackgroundSelf-citationWigton, R., Radua, J., Allen, P., Averbeck, B., Meyer-Lindenberg, A., McGuire, P., Shergill, S. S., & Fusar-Poli, P. (2015) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.130289 · Cited by 179 · see citing works
Quintana, D. S., Guastella, A. J., Westlye, L. T., & Andreassen, O. A. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.166 · Cited by 107 · see citing works
Oxytocin receptor dynamics in the brain across development and species
Vaidyanathan, R., & Hammock, E. A. D. (2016) · Developmental Neurobiology · doi:10.1002/dneu.22403 · Cited by 82 · see citing works
Numan, M. (2020) · doi:10.1093/oso/9780190848675.001.0001 · Cited by 101 · see citing works
Kohli, S., King, M. V., Williams, S. A., Edwards, A., Ballard, T. M., Steward, L. J., Alberati, D., & Fone, K. C. F. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0171-0 · Cited by 60 · see citing works
Amino sulfonic acids, peptidosulfonamides and other related compounds
Grygorenko, O. O., Biitseva, A. V., & Zhersh, S. (2018) · Tetrahedron · doi:10.1016/j.tet.2018.01.033 · Cited by 53 · 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-citationGuoynes, C. D., Simmons, T. C., Downing, G., Jacob, S., Solomon, M., & Bales, K. L. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.11.037 · Cited by 38 · see citing works
Smith, A. L., Freeman, S. M., Barnhart, T. E., Abbott, D. H., Ahlers, E. O., Kukis, D. L., Bales, K. L., Goodman, M. M., & Young, L. J. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.04.097 · Cited by 29 · see citing works
Self-citationInvestigation 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-citationWenzel, B., Mollitor, J., Deuther‐Conrad, W., Dukić-Stefanović, S., Kranz, M., Vraka, C., Teodoro, R., Günther, R., Donat, C. K., Ludwig, F., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01080 · Cited by 21 · see citing works
Watanasriyakul, W. T., Scotti, M. L., Carter, C. S., McNeal, N., Colburn, W., Wardwell, J., & Grippo, A. J. (2022) · Autonomic Neuroscience · doi:10.1016/j.autneu.2022.102967 · Cited by 14 · see citing works
Smith, A. L., Walum, H., Connor‐Stroud, F., Freeman, S. M., Inoue, K., Parr, L. A., Goodman, M. M., & Young, L. J. (2016) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2016.10.035 · Cited by 9 · see citing works
Self-citationVidal, B., Karpenko, J., Liger, F., Fieux, S., Bouillot, C., Billard, T., Hibert, M., & Zimmer, L. (2017) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2017.07.008 · Cited by 7 · see citing works
Freeman, S. M. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1759-5_7 · Cited by 7 · see citing works
Self-citationMarzano, C., Jakobsen, S., Salinas, C. A., Tang, S. P., Bender, D., Passchier, J., & Plisson, C. (2017) · Journal of Labelled Compounds and Radiopharmaceuticals · doi:10.1002/jlcr.3535 · Cited by 3 · see citing works
Freeman, S. M., Catrow, J. L., Cox, J. E., Turano, A., Rich, M. A., Ihrig, H. P., Poudyal, N., Chang, C. T., Gese, E. M., Young, J. K., et al. (2024) · Comparative Medicine · doi:10.30802/aalas-cm-23-000044 · Cited by 2 · see citing works
Self-citationNuman, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0008 · Cited by 2 · see citing works
Hormonal Control of Maternal Behavior in Nonhuman Mammals
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0003 · Cited by 2 · see citing works
Guastella, A. J., Alvares, G. A., Hickie, I. B., Chan, H., Chen, T. F., & Banati, R. B. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.03.005 · Cited by 2 · see citing works
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0002 · Cited by 1 · see citing works
Development and characterisation of novel oxytocin analogues for PET imaging
Pascali, G., Parmar, A., Zanoni, S., Arthur, A., Hering, A., Teakle, N., Markham, J. W., Zhang, B., Mackay, T., Klenner, M. A., et al. (2025) · Communications Chemistry · doi:10.1038/s42004-025-01649-1 · Cited by 1 · see citing works
Self-citationNuman, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0001 · Cited by 1 · see citing works
Central Neural Circuits Regulating Maternal Behavior in Nonhuman Mammals
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0005 · Cited by 1 · see citing works
Alloparental Behavior and Paternal Behavior in Nonhuman Mammals
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0007 · Cited by 1 · see citing works
Oxytocin, Vasopressin, and Development of Social Behavior in Primates
Bales, K. L. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-804042-3.00094-4
Evolutionary Perspectives on the Parental Brain
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0011
Anxiety Reduction and Maternal Aggression in Postpartum Nonhuman Mammals
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0006
Development of the Parental Brain in Nonhuman Mammals
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0009
Development of the Parental Brain in Humans
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0010
Brain Mechanisms Regulating Maternal Behavior in Nonhuman Mammals
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0004
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.002.0006
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.002.0003
Abbreviations Used for Major Brain Regions
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.002.0007
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.002.0004
BindingDB (2014) · UC San Diego · doi:10.7270/q20r9qvh
- Authors
- Smith, A. L., Freeman, S. M., Voll, R. J., Young, L. J., & Goodman, M. M.
- Affiliations
- Emory University (US)
- Emory National Primate Research Center (US)
- Corresponding author
- Goodman, Mark M.
- Venue
- Bioorganic & Medicinal Chemistry Letters
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 23
- Issue
- 3
- Pages
- 902-906
- ISSN
- 0960-894X (ISSN-L)
- PMC
- PMC3756487
- OpenAlex
- W2007002339
- Cited by
- 38
- References
- 24
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 1 · 2021: 1 · 2020: 16 · 2018: 2 · 2017: 3 · 2016: 7 · 2015: 3 · 2014: 1 · 2013: 2
- FWCI
- 1.69
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Bioorganic & Medicinal Chemistry Letters (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (P51OD011132)
- University of North Carolina at Chapel Hill
- National Institute of Mental Health (K02MH064692, MH064692, R21MH090776)
- National Center for Research Resources (P51RR165)
- 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
- L-368,899, oxytocin receptor, carbon-11 radiolabeling, positron emission tomography, brain penetration, receptor antagonists, choroid plexus, Macaca fascicularis, rats
- MeSH terms
- Alkylation, Animals, Camphanes, Brain, Carbon Radioisotopes, Macaca fascicularis, Piperazines, Sensory Receptor Cells, Molecular Structure, Receptors, Oxytocin, Radiopharmaceuticals, Models, Animal, 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
