Estimation of target occupancy in repeated dosing design studies using positron emission tomography: Biases due to target upregulation Article Swipe
Eugenii A. Rabiner
,
Roger N. Gunn
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1177/0271678x231214443
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1177/0271678x231214443
Positron emission tomography (PET) has become indispensable in the quantification of target engagement by brain targeting medications. The relationship between the drug plasma concentration (or drug dose administered) and target occupancy determined during a PET occupancy study has provided valuable information for the assessment of novel pharmaceuticals in the early phases of drug development. Such information is also critical for the understanding of the mechanisms of action and side-effect profile of approved medication commonly used in the clinic. Occupancy studies conducted following repeated drug dosing (RD) can produce systematic differences from those conducted following single drug dose (SD), differences that have not been adequately explored. We have hypothesised that when differences are observed between RD and SD studies, they are related to changes in target density induced by repeated drug accumulation. We have developed a modified occupancy model to account for potential changes in target density and tested it on a sample dataset. We found that target upregulation can parsimoniously explain the differences in drug affinity estimated in SD and RD studies. Our findings have implications for the interpretation of RD occupancy data in the literature and the relationship between specific target occupancy levels and drug efficacy and tolerability.
Related Topics
Concepts
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1177/0271678x231214443
- OA Status
- green
- Cited By
- 2
- References
- 31
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4388516834
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4388516834Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1177/0271678x231214443Digital Object Identifier
- Title
-
Estimation of target occupancy in repeated dosing design studies using positron emission tomography: Biases due to target upregulationWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-11-09Full publication date if available
- Authors
-
Eugenii A. Rabiner, Roger N. GunnList of authors in order
- Landing page
-
https://doi.org/10.1177/0271678x231214443Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.ncbi.nlm.nih.gov/pmc/articles/10981403Direct OA link when available
- Concepts
-
Occupancy, Positron emission tomography, Dosing, Drug, Drug development, Pharmacology, Tolerability, Medicine, Downregulation and upregulation, Medical physics, Nuclear medicine, Adverse effect, Chemistry, Biology, Ecology, Biochemistry, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
2Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 2Per-year citation counts (last 5 years)
- References (count)
-
31Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
Full payload
| id | https://openalex.org/W4388516834 |
|---|---|
| doi | https://doi.org/10.1177/0271678x231214443 |
| ids.doi | https://doi.org/10.1177/0271678x231214443 |
| ids.pmid | https://pubmed.ncbi.nlm.nih.gov/37944261 |
| ids.openalex | https://openalex.org/W4388516834 |
| fwci | 0.7557951 |
| mesh[0].qualifier_ui | |
| mesh[0].descriptor_ui | D015854 |
| mesh[0].is_major_topic | False |
| mesh[0].qualifier_name | |
| mesh[0].descriptor_name | Up-Regulation |
| mesh[1].qualifier_ui | |
| mesh[1].descriptor_ui | D049268 |
| mesh[1].is_major_topic | True |
| mesh[1].qualifier_name | |
| mesh[1].descriptor_name | Positron-Emission Tomography |
| mesh[2].qualifier_ui | Q000378 |
| mesh[2].descriptor_ui | D001921 |
| mesh[2].is_major_topic | True |
| mesh[2].qualifier_name | metabolism |
| mesh[2].descriptor_name | Brain |
| mesh[3].qualifier_ui | |
| mesh[3].descriptor_ui | D015982 |
| mesh[3].is_major_topic | False |
| mesh[3].qualifier_name | |
| mesh[3].descriptor_name | Bias |
| mesh[4].qualifier_ui | |
| mesh[4].descriptor_ui | D004305 |
| mesh[4].is_major_topic | False |
| mesh[4].qualifier_name | |
| mesh[4].descriptor_name | Dose-Response Relationship, Drug |
| mesh[5].qualifier_ui | |
| mesh[5].descriptor_ui | D015854 |
| mesh[5].is_major_topic | False |
| mesh[5].qualifier_name | |
| mesh[5].descriptor_name | Up-Regulation |
| mesh[6].qualifier_ui | |
| mesh[6].descriptor_ui | D049268 |
| mesh[6].is_major_topic | True |
| mesh[6].qualifier_name | |
| mesh[6].descriptor_name | Positron-Emission Tomography |
| mesh[7].qualifier_ui | Q000378 |
| mesh[7].descriptor_ui | D001921 |
| mesh[7].is_major_topic | True |
| mesh[7].qualifier_name | metabolism |
| mesh[7].descriptor_name | Brain |
| mesh[8].qualifier_ui | |
| mesh[8].descriptor_ui | D015982 |
| mesh[8].is_major_topic | False |
| mesh[8].qualifier_name | |
| mesh[8].descriptor_name | Bias |
| mesh[9].qualifier_ui | |
| mesh[9].descriptor_ui | D004305 |
| mesh[9].is_major_topic | False |
| mesh[9].qualifier_name | |
| mesh[9].descriptor_name | Dose-Response Relationship, Drug |
| mesh[10].qualifier_ui | |
| mesh[10].descriptor_ui | D015854 |
| mesh[10].is_major_topic | False |
| mesh[10].qualifier_name | |
| mesh[10].descriptor_name | Up-Regulation |
| mesh[11].qualifier_ui | |
| mesh[11].descriptor_ui | D049268 |
| mesh[11].is_major_topic | True |
| mesh[11].qualifier_name | |
| mesh[11].descriptor_name | Positron-Emission Tomography |
| mesh[12].qualifier_ui | Q000378 |
| mesh[12].descriptor_ui | D001921 |
| mesh[12].is_major_topic | True |
| mesh[12].qualifier_name | metabolism |
| mesh[12].descriptor_name | Brain |
| mesh[13].qualifier_ui | |
| mesh[13].descriptor_ui | D015982 |
| mesh[13].is_major_topic | False |
| mesh[13].qualifier_name | |
| mesh[13].descriptor_name | Bias |
| mesh[14].qualifier_ui | |
| mesh[14].descriptor_ui | D004305 |
| mesh[14].is_major_topic | False |
| mesh[14].qualifier_name | |
| mesh[14].descriptor_name | Dose-Response Relationship, Drug |
| mesh[15].qualifier_ui | |
| mesh[15].descriptor_ui | D015854 |
| mesh[15].is_major_topic | False |
| mesh[15].qualifier_name | |
| mesh[15].descriptor_name | Up-Regulation |
| mesh[16].qualifier_ui | |
| mesh[16].descriptor_ui | D049268 |
| mesh[16].is_major_topic | True |
| mesh[16].qualifier_name | |
| mesh[16].descriptor_name | Positron-Emission Tomography |
| mesh[17].qualifier_ui | Q000378 |
| mesh[17].descriptor_ui | D001921 |
| mesh[17].is_major_topic | True |
| mesh[17].qualifier_name | metabolism |
| mesh[17].descriptor_name | Brain |
| mesh[18].qualifier_ui | |
| mesh[18].descriptor_ui | D015982 |
| mesh[18].is_major_topic | False |
| mesh[18].qualifier_name | |
| mesh[18].descriptor_name | Bias |
| mesh[19].qualifier_ui | |
| mesh[19].descriptor_ui | D004305 |
| mesh[19].is_major_topic | False |
| mesh[19].qualifier_name | |
| mesh[19].descriptor_name | Dose-Response Relationship, Drug |
| mesh[20].qualifier_ui | |
| mesh[20].descriptor_ui | D015854 |
| mesh[20].is_major_topic | False |
| mesh[20].qualifier_name | |
| mesh[20].descriptor_name | Up-Regulation |
| mesh[21].qualifier_ui | |
| mesh[21].descriptor_ui | D049268 |
| mesh[21].is_major_topic | True |
| mesh[21].qualifier_name | |
| mesh[21].descriptor_name | Positron-Emission Tomography |
| mesh[22].qualifier_ui | Q000378 |
| mesh[22].descriptor_ui | D001921 |
| mesh[22].is_major_topic | True |
| mesh[22].qualifier_name | metabolism |
| mesh[22].descriptor_name | Brain |
| mesh[23].qualifier_ui | |
| mesh[23].descriptor_ui | D015982 |
| mesh[23].is_major_topic | False |
| mesh[23].qualifier_name | |
| mesh[23].descriptor_name | Bias |
| mesh[24].qualifier_ui | |
| mesh[24].descriptor_ui | D004305 |
| mesh[24].is_major_topic | False |
| mesh[24].qualifier_name | |
| mesh[24].descriptor_name | Dose-Response Relationship, Drug |
| mesh[25].qualifier_ui | |
| mesh[25].descriptor_ui | D015854 |
| mesh[25].is_major_topic | False |
| mesh[25].qualifier_name | |
| mesh[25].descriptor_name | Up-Regulation |
| mesh[26].qualifier_ui | |
| mesh[26].descriptor_ui | D049268 |
| mesh[26].is_major_topic | True |
| mesh[26].qualifier_name | |
| mesh[26].descriptor_name | Positron-Emission Tomography |
| mesh[27].qualifier_ui | Q000378 |
| mesh[27].descriptor_ui | D001921 |
| mesh[27].is_major_topic | True |
| mesh[27].qualifier_name | metabolism |
| mesh[27].descriptor_name | Brain |
| mesh[28].qualifier_ui | |
| mesh[28].descriptor_ui | D015982 |
| mesh[28].is_major_topic | False |
| mesh[28].qualifier_name | |
| mesh[28].descriptor_name | Bias |
| mesh[29].qualifier_ui | |
| mesh[29].descriptor_ui | D004305 |
| mesh[29].is_major_topic | False |
| mesh[29].qualifier_name | |
| mesh[29].descriptor_name | Dose-Response Relationship, Drug |
| type | article |
| title | Estimation of target occupancy in repeated dosing design studies using positron emission tomography: Biases due to target upregulation |
| biblio.issue | 4 |
| biblio.volume | 44 |
| biblio.last_page | 579 |
| biblio.first_page | 573 |
| topics[0].id | https://openalex.org/T10854 |
| topics[0].field.id | https://openalex.org/fields/27 |
| topics[0].field.display_name | Medicine |
| topics[0].score | 0.9987000226974487 |
| topics[0].domain.id | https://openalex.org/domains/4 |
| topics[0].domain.display_name | Health Sciences |
| topics[0].subfield.id | https://openalex.org/subfields/2738 |
| topics[0].subfield.display_name | Psychiatry and Mental health |
| topics[0].display_name | Bipolar Disorder and Treatment |
| topics[1].id | https://openalex.org/T11071 |
| topics[1].field.id | https://openalex.org/fields/27 |
| topics[1].field.display_name | Medicine |
| topics[1].score | 0.9977999925613403 |
| topics[1].domain.id | https://openalex.org/domains/4 |
| topics[1].domain.display_name | Health Sciences |
| topics[1].subfield.id | https://openalex.org/subfields/2736 |
| topics[1].subfield.display_name | Pharmacology |
| topics[1].display_name | Treatment of Major Depression |
| topics[2].id | https://openalex.org/T12434 |
| topics[2].field.id | https://openalex.org/fields/13 |
| topics[2].field.display_name | Biochemistry, Genetics and Molecular Biology |
| topics[2].score | 0.9972000122070312 |
| topics[2].domain.id | https://openalex.org/domains/1 |
| topics[2].domain.display_name | Life Sciences |
| topics[2].subfield.id | https://openalex.org/subfields/1312 |
| topics[2].subfield.display_name | Molecular Biology |
| topics[2].display_name | Phosphodiesterase function and regulation |
| is_xpac | False |
| apc_list | |
| apc_paid | |
| concepts[0].id | https://openalex.org/C160331591 |
| concepts[0].level | 2 |
| concepts[0].score | 0.828743577003479 |
| concepts[0].wikidata | https://www.wikidata.org/wiki/Q7075743 |
| concepts[0].display_name | Occupancy |
| concepts[1].id | https://openalex.org/C2775842073 |
| concepts[1].level | 2 |
| concepts[1].score | 0.7619955539703369 |
| concepts[1].wikidata | https://www.wikidata.org/wiki/Q208376 |
| concepts[1].display_name | Positron emission tomography |
| concepts[2].id | https://openalex.org/C2777288759 |
| concepts[2].level | 2 |
| concepts[2].score | 0.6838654279708862 |
| concepts[2].wikidata | https://www.wikidata.org/wiki/Q4164182 |
| concepts[2].display_name | Dosing |
| concepts[3].id | https://openalex.org/C2780035454 |
| concepts[3].level | 2 |
| concepts[3].score | 0.5957320928573608 |
| concepts[3].wikidata | https://www.wikidata.org/wiki/Q8386 |
| concepts[3].display_name | Drug |
| concepts[4].id | https://openalex.org/C64903051 |
| concepts[4].level | 3 |
| concepts[4].score | 0.5383305549621582 |
| concepts[4].wikidata | https://www.wikidata.org/wiki/Q2198549 |
| concepts[4].display_name | Drug development |
| concepts[5].id | https://openalex.org/C98274493 |
| concepts[5].level | 1 |
| concepts[5].score | 0.5353453755378723 |
| concepts[5].wikidata | https://www.wikidata.org/wiki/Q128406 |
| concepts[5].display_name | Pharmacology |
| concepts[6].id | https://openalex.org/C2778375690 |
| concepts[6].level | 3 |
| concepts[6].score | 0.5161219835281372 |
| concepts[6].wikidata | https://www.wikidata.org/wiki/Q7814214 |
| concepts[6].display_name | Tolerability |
| concepts[7].id | https://openalex.org/C71924100 |
| concepts[7].level | 0 |
| concepts[7].score | 0.47776639461517334 |
| concepts[7].wikidata | https://www.wikidata.org/wiki/Q11190 |
| concepts[7].display_name | Medicine |
| concepts[8].id | https://openalex.org/C127561419 |
| concepts[8].level | 3 |
| concepts[8].score | 0.42513507604599 |
| concepts[8].wikidata | https://www.wikidata.org/wiki/Q224527 |
| concepts[8].display_name | Downregulation and upregulation |
| concepts[9].id | https://openalex.org/C19527891 |
| concepts[9].level | 1 |
| concepts[9].score | 0.3296249508857727 |
| concepts[9].wikidata | https://www.wikidata.org/wiki/Q1120908 |
| concepts[9].display_name | Medical physics |
| concepts[10].id | https://openalex.org/C2989005 |
| concepts[10].level | 1 |
| concepts[10].score | 0.2875116467475891 |
| concepts[10].wikidata | https://www.wikidata.org/wiki/Q214963 |
| concepts[10].display_name | Nuclear medicine |
| concepts[11].id | https://openalex.org/C197934379 |
| concepts[11].level | 2 |
| concepts[11].score | 0.18690967559814453 |
| concepts[11].wikidata | https://www.wikidata.org/wiki/Q2047938 |
| concepts[11].display_name | Adverse effect |
| concepts[12].id | https://openalex.org/C185592680 |
| concepts[12].level | 0 |
| concepts[12].score | 0.14622101187705994 |
| concepts[12].wikidata | https://www.wikidata.org/wiki/Q2329 |
| concepts[12].display_name | Chemistry |
| concepts[13].id | https://openalex.org/C86803240 |
| concepts[13].level | 0 |
| concepts[13].score | 0.08917292952537537 |
| concepts[13].wikidata | https://www.wikidata.org/wiki/Q420 |
| concepts[13].display_name | Biology |
| concepts[14].id | https://openalex.org/C18903297 |
| concepts[14].level | 1 |
| concepts[14].score | 0.0 |
| concepts[14].wikidata | https://www.wikidata.org/wiki/Q7150 |
| concepts[14].display_name | Ecology |
| concepts[15].id | https://openalex.org/C55493867 |
| concepts[15].level | 1 |
| concepts[15].score | 0.0 |
| concepts[15].wikidata | https://www.wikidata.org/wiki/Q7094 |
| concepts[15].display_name | Biochemistry |
| concepts[16].id | https://openalex.org/C104317684 |
| concepts[16].level | 2 |
| concepts[16].score | 0.0 |
| concepts[16].wikidata | https://www.wikidata.org/wiki/Q7187 |
| concepts[16].display_name | Gene |
| keywords[0].id | https://openalex.org/keywords/occupancy |
| keywords[0].score | 0.828743577003479 |
| keywords[0].display_name | Occupancy |
| keywords[1].id | https://openalex.org/keywords/positron-emission-tomography |
| keywords[1].score | 0.7619955539703369 |
| keywords[1].display_name | Positron emission tomography |
| keywords[2].id | https://openalex.org/keywords/dosing |
| keywords[2].score | 0.6838654279708862 |
| keywords[2].display_name | Dosing |
| keywords[3].id | https://openalex.org/keywords/drug |
| keywords[3].score | 0.5957320928573608 |
| keywords[3].display_name | Drug |
| keywords[4].id | https://openalex.org/keywords/drug-development |
| keywords[4].score | 0.5383305549621582 |
| keywords[4].display_name | Drug development |
| keywords[5].id | https://openalex.org/keywords/pharmacology |
| keywords[5].score | 0.5353453755378723 |
| keywords[5].display_name | Pharmacology |
| keywords[6].id | https://openalex.org/keywords/tolerability |
| keywords[6].score | 0.5161219835281372 |
| keywords[6].display_name | Tolerability |
| keywords[7].id | https://openalex.org/keywords/medicine |
| keywords[7].score | 0.47776639461517334 |
| keywords[7].display_name | Medicine |
| keywords[8].id | https://openalex.org/keywords/downregulation-and-upregulation |
| keywords[8].score | 0.42513507604599 |
| keywords[8].display_name | Downregulation and upregulation |
| keywords[9].id | https://openalex.org/keywords/medical-physics |
| keywords[9].score | 0.3296249508857727 |
| keywords[9].display_name | Medical physics |
| keywords[10].id | https://openalex.org/keywords/nuclear-medicine |
| keywords[10].score | 0.2875116467475891 |
| keywords[10].display_name | Nuclear medicine |
| keywords[11].id | https://openalex.org/keywords/adverse-effect |
| keywords[11].score | 0.18690967559814453 |
| keywords[11].display_name | Adverse effect |
| keywords[12].id | https://openalex.org/keywords/chemistry |
| keywords[12].score | 0.14622101187705994 |
| keywords[12].display_name | Chemistry |
| keywords[13].id | https://openalex.org/keywords/biology |
| keywords[13].score | 0.08917292952537537 |
| keywords[13].display_name | Biology |
| language | en |
| locations[0].id | doi:10.1177/0271678x231214443 |
| locations[0].is_oa | False |
| locations[0].source.id | https://openalex.org/S89339265 |
| locations[0].source.issn | 0271-678X, 1559-7016 |
| locations[0].source.type | journal |
| locations[0].source.is_oa | False |
| locations[0].source.issn_l | 0271-678X |
| locations[0].source.is_core | True |
| locations[0].source.is_in_doaj | False |
| locations[0].source.display_name | Journal of Cerebral Blood Flow & Metabolism |
| locations[0].source.host_organization | https://openalex.org/P4310320017 |
| locations[0].source.host_organization_name | SAGE Publishing |
| locations[0].source.host_organization_lineage | https://openalex.org/P4310320017 |
| locations[0].source.host_organization_lineage_names | SAGE Publishing |
| locations[0].license | |
| locations[0].pdf_url | |
| locations[0].version | publishedVersion |
| locations[0].raw_type | journal-article |
| locations[0].license_id | |
| locations[0].is_accepted | True |
| locations[0].is_published | True |
| locations[0].raw_source_name | Journal of Cerebral Blood Flow & Metabolism |
| locations[0].landing_page_url | https://doi.org/10.1177/0271678x231214443 |
| locations[1].id | pmid:37944261 |
| locations[1].is_oa | False |
| locations[1].source.id | https://openalex.org/S4306525036 |
| locations[1].source.issn | |
| locations[1].source.type | repository |
| locations[1].source.is_oa | False |
| locations[1].source.issn_l | |
| locations[1].source.is_core | False |
| locations[1].source.is_in_doaj | False |
| locations[1].source.display_name | PubMed |
| locations[1].source.host_organization | https://openalex.org/I1299303238 |
| locations[1].source.host_organization_name | National Institutes of Health |
| locations[1].source.host_organization_lineage | https://openalex.org/I1299303238 |
| locations[1].license | |
| locations[1].pdf_url | |
| locations[1].version | publishedVersion |
| locations[1].raw_type | |
| locations[1].license_id | |
| locations[1].is_accepted | True |
| locations[1].is_published | True |
| locations[1].raw_source_name | Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism |
| locations[1].landing_page_url | https://pubmed.ncbi.nlm.nih.gov/37944261 |
| locations[2].id | pmh:oai:pubmedcentral.nih.gov:10981403 |
| locations[2].is_oa | True |
| locations[2].source.id | https://openalex.org/S2764455111 |
| locations[2].source.issn | |
| locations[2].source.type | repository |
| locations[2].source.is_oa | False |
| locations[2].source.issn_l | |
| locations[2].source.is_core | False |
| locations[2].source.is_in_doaj | False |
| locations[2].source.display_name | PubMed Central |
| locations[2].source.host_organization | https://openalex.org/I1299303238 |
| locations[2].source.host_organization_name | National Institutes of Health |
| locations[2].source.host_organization_lineage | https://openalex.org/I1299303238 |
| locations[2].license | |
| locations[2].pdf_url | |
| locations[2].version | submittedVersion |
| locations[2].raw_type | Text |
| locations[2].license_id | |
| locations[2].is_accepted | False |
| locations[2].is_published | False |
| locations[2].raw_source_name | J Cereb Blood Flow Metab |
| locations[2].landing_page_url | https://www.ncbi.nlm.nih.gov/pmc/articles/10981403 |
| indexed_in | crossref, pubmed |
| authorships[0].author.id | https://openalex.org/A5005098704 |
| authorships[0].author.orcid | https://orcid.org/0000-0003-3612-6687 |
| authorships[0].author.display_name | Eugenii A. Rabiner |
| authorships[0].countries | GB |
| authorships[0].affiliations[0].institution_ids | https://openalex.org/I4210093835 |
| authorships[0].affiliations[0].raw_affiliation_string | Invicro, London, UK |
| authorships[0].institutions[0].id | https://openalex.org/I4210093835 |
| authorships[0].institutions[0].ror | https://ror.org/00gssft54 |
| authorships[0].institutions[0].type | company |
| authorships[0].institutions[0].lineage | https://openalex.org/I4210093835 |
| authorships[0].institutions[0].country_code | GB |
| authorships[0].institutions[0].display_name | Invicro (United Kingdom) |
| authorships[0].author_position | first |
| authorships[0].raw_author_name | Eugenii A Rabiner |
| authorships[0].is_corresponding | True |
| authorships[0].raw_affiliation_strings | Invicro, London, UK |
| authorships[1].author.id | https://openalex.org/A5065874626 |
| authorships[1].author.orcid | https://orcid.org/0000-0003-1181-5769 |
| authorships[1].author.display_name | Roger N. Gunn |
| authorships[1].countries | GB |
| authorships[1].affiliations[0].institution_ids | https://openalex.org/I4210093835 |
| authorships[1].affiliations[0].raw_affiliation_string | Invicro, London, UK |
| authorships[1].affiliations[1].institution_ids | https://openalex.org/I47508984 |
| authorships[1].affiliations[1].raw_affiliation_string | Department of Brain Sciences, Imperial College London, London, UK |
| authorships[1].institutions[0].id | https://openalex.org/I47508984 |
| authorships[1].institutions[0].ror | https://ror.org/041kmwe10 |
| authorships[1].institutions[0].type | education |
| authorships[1].institutions[0].lineage | https://openalex.org/I47508984 |
| authorships[1].institutions[0].country_code | GB |
| authorships[1].institutions[0].display_name | Imperial College London |
| authorships[1].institutions[1].id | https://openalex.org/I4210093835 |
| authorships[1].institutions[1].ror | https://ror.org/00gssft54 |
| authorships[1].institutions[1].type | company |
| authorships[1].institutions[1].lineage | https://openalex.org/I4210093835 |
| authorships[1].institutions[1].country_code | GB |
| authorships[1].institutions[1].display_name | Invicro (United Kingdom) |
| authorships[1].author_position | last |
| authorships[1].raw_author_name | Roger N Gunn |
| authorships[1].is_corresponding | False |
| authorships[1].raw_affiliation_strings | Department of Brain Sciences, Imperial College London, London, UK, Invicro, London, UK |
| has_content.pdf | False |
| has_content.grobid_xml | False |
| is_paratext | False |
| open_access.is_oa | True |
| open_access.oa_url | https://www.ncbi.nlm.nih.gov/pmc/articles/10981403 |
| open_access.oa_status | green |
| open_access.any_repository_has_fulltext | False |
| created_date | 2025-10-10T00:00:00 |
| display_name | Estimation of target occupancy in repeated dosing design studies using positron emission tomography: Biases due to target upregulation |
| has_fulltext | False |
| is_retracted | False |
| updated_date | 2025-11-06T03:46:38.306776 |
| primary_topic.id | https://openalex.org/T10854 |
| primary_topic.field.id | https://openalex.org/fields/27 |
| primary_topic.field.display_name | Medicine |
| primary_topic.score | 0.9987000226974487 |
| primary_topic.domain.id | https://openalex.org/domains/4 |
| primary_topic.domain.display_name | Health Sciences |
| primary_topic.subfield.id | https://openalex.org/subfields/2738 |
| primary_topic.subfield.display_name | Psychiatry and Mental health |
| primary_topic.display_name | Bipolar Disorder and Treatment |
| related_works | https://openalex.org/W4282043467, https://openalex.org/W4311628015, https://openalex.org/W3191427281, https://openalex.org/W2105697914, https://openalex.org/W3093197249, https://openalex.org/W1968324288, https://openalex.org/W2087016115, https://openalex.org/W2305775430, https://openalex.org/W2783315223, https://openalex.org/W1540010871 |
| cited_by_count | 2 |
| counts_by_year[0].year | 2025 |
| counts_by_year[0].cited_by_count | 2 |
| locations_count | 3 |
| best_oa_location.id | pmh:oai:pubmedcentral.nih.gov:10981403 |
| best_oa_location.is_oa | True |
| best_oa_location.source.id | https://openalex.org/S2764455111 |
| best_oa_location.source.issn | |
| best_oa_location.source.type | repository |
| best_oa_location.source.is_oa | False |
| best_oa_location.source.issn_l | |
| best_oa_location.source.is_core | False |
| best_oa_location.source.is_in_doaj | False |
| best_oa_location.source.display_name | PubMed Central |
| best_oa_location.source.host_organization | https://openalex.org/I1299303238 |
| best_oa_location.source.host_organization_name | National Institutes of Health |
| best_oa_location.source.host_organization_lineage | https://openalex.org/I1299303238 |
| best_oa_location.license | |
| best_oa_location.pdf_url | |
| best_oa_location.version | submittedVersion |
| best_oa_location.raw_type | Text |
| best_oa_location.license_id | |
| best_oa_location.is_accepted | False |
| best_oa_location.is_published | False |
| best_oa_location.raw_source_name | J Cereb Blood Flow Metab |
| best_oa_location.landing_page_url | https://www.ncbi.nlm.nih.gov/pmc/articles/10981403 |
| primary_location.id | doi:10.1177/0271678x231214443 |
| primary_location.is_oa | False |
| primary_location.source.id | https://openalex.org/S89339265 |
| primary_location.source.issn | 0271-678X, 1559-7016 |
| primary_location.source.type | journal |
| primary_location.source.is_oa | False |
| primary_location.source.issn_l | 0271-678X |
| primary_location.source.is_core | True |
| primary_location.source.is_in_doaj | False |
| primary_location.source.display_name | Journal of Cerebral Blood Flow & Metabolism |
| primary_location.source.host_organization | https://openalex.org/P4310320017 |
| primary_location.source.host_organization_name | SAGE Publishing |
| primary_location.source.host_organization_lineage | https://openalex.org/P4310320017 |
| primary_location.source.host_organization_lineage_names | SAGE Publishing |
| primary_location.license | |
| primary_location.pdf_url | |
| primary_location.version | publishedVersion |
| primary_location.raw_type | journal-article |
| primary_location.license_id | |
| primary_location.is_accepted | True |
| primary_location.is_published | True |
| primary_location.raw_source_name | Journal of Cerebral Blood Flow & Metabolism |
| primary_location.landing_page_url | https://doi.org/10.1177/0271678x231214443 |
| publication_date | 2023-11-09 |
| publication_year | 2023 |
| referenced_works | https://openalex.org/W2077885318, https://openalex.org/W2543692442, https://openalex.org/W3174054264, https://openalex.org/W2058690393, https://openalex.org/W2056527144, https://openalex.org/W2112278807, https://openalex.org/W2134284299, https://openalex.org/W2048580544, https://openalex.org/W2072069319, https://openalex.org/W2315029279, https://openalex.org/W2034861437, https://openalex.org/W2099185967, https://openalex.org/W2003821327, https://openalex.org/W1964544578, https://openalex.org/W2019648896, https://openalex.org/W2053436533, https://openalex.org/W2126097234, https://openalex.org/W2161951768, https://openalex.org/W2075412000, https://openalex.org/W2408118828, https://openalex.org/W2074140506, https://openalex.org/W2068346256, https://openalex.org/W2002689986, https://openalex.org/W2096271770, https://openalex.org/W2523139904, https://openalex.org/W2095369944, https://openalex.org/W2983974020, https://openalex.org/W1978543620, https://openalex.org/W2130624752, https://openalex.org/W1949553311, https://openalex.org/W4206224349 |
| referenced_works_count | 31 |
| abstract_inverted_index.a | 33, 134, 150 |
| abstract_inverted_index.RD | 114, 170, 180 |
| abstract_inverted_index.SD | 116, 168 |
| abstract_inverted_index.We | 105, 131, 153 |
| abstract_inverted_index.by | 13, 127 |
| abstract_inverted_index.in | 7, 47, 75, 123, 143, 163, 167, 183 |
| abstract_inverted_index.is | 56 |
| abstract_inverted_index.it | 148 |
| abstract_inverted_index.of | 10, 44, 51, 62, 65, 70, 179 |
| abstract_inverted_index.on | 149 |
| abstract_inverted_index.to | 121, 138 |
| abstract_inverted_index.(or | 24 |
| abstract_inverted_index.Our | 172 |
| abstract_inverted_index.PET | 34 |
| abstract_inverted_index.The | 17 |
| abstract_inverted_index.and | 28, 67, 115, 146, 169, 186, 194, 197 |
| abstract_inverted_index.are | 111, 119 |
| abstract_inverted_index.can | 86, 158 |
| abstract_inverted_index.for | 41, 59, 140, 176 |
| abstract_inverted_index.has | 4, 37 |
| abstract_inverted_index.not | 101 |
| abstract_inverted_index.the | 8, 20, 42, 48, 60, 63, 76, 161, 177, 184, 187 |
| abstract_inverted_index.(RD) | 85 |
| abstract_inverted_index.Such | 54 |
| abstract_inverted_index.also | 57 |
| abstract_inverted_index.been | 102 |
| abstract_inverted_index.data | 182 |
| abstract_inverted_index.dose | 26, 96 |
| abstract_inverted_index.drug | 21, 25, 52, 83, 95, 129, 164, 195 |
| abstract_inverted_index.from | 90 |
| abstract_inverted_index.have | 100, 106, 132, 174 |
| abstract_inverted_index.that | 99, 108, 155 |
| abstract_inverted_index.they | 118 |
| abstract_inverted_index.used | 74 |
| abstract_inverted_index.when | 109 |
| abstract_inverted_index.(PET) | 3 |
| abstract_inverted_index.(SD), | 97 |
| abstract_inverted_index.brain | 14 |
| abstract_inverted_index.early | 49 |
| abstract_inverted_index.found | 154 |
| abstract_inverted_index.model | 137 |
| abstract_inverted_index.novel | 45 |
| abstract_inverted_index.study | 36 |
| abstract_inverted_index.those | 91 |
| abstract_inverted_index.action | 66 |
| abstract_inverted_index.become | 5 |
| abstract_inverted_index.dosing | 84 |
| abstract_inverted_index.during | 32 |
| abstract_inverted_index.levels | 193 |
| abstract_inverted_index.phases | 50 |
| abstract_inverted_index.plasma | 22 |
| abstract_inverted_index.sample | 151 |
| abstract_inverted_index.single | 94 |
| abstract_inverted_index.target | 11, 29, 124, 144, 156, 191 |
| abstract_inverted_index.tested | 147 |
| abstract_inverted_index.account | 139 |
| abstract_inverted_index.between | 19, 113, 189 |
| abstract_inverted_index.changes | 122, 142 |
| abstract_inverted_index.clinic. | 77 |
| abstract_inverted_index.density | 125, 145 |
| abstract_inverted_index.explain | 160 |
| abstract_inverted_index.induced | 126 |
| abstract_inverted_index.produce | 87 |
| abstract_inverted_index.profile | 69 |
| abstract_inverted_index.related | 120 |
| abstract_inverted_index.studies | 79 |
| abstract_inverted_index.Positron | 0 |
| abstract_inverted_index.affinity | 165 |
| abstract_inverted_index.approved | 71 |
| abstract_inverted_index.commonly | 73 |
| abstract_inverted_index.critical | 58 |
| abstract_inverted_index.dataset. | 152 |
| abstract_inverted_index.efficacy | 196 |
| abstract_inverted_index.emission | 1 |
| abstract_inverted_index.findings | 173 |
| abstract_inverted_index.modified | 135 |
| abstract_inverted_index.observed | 112 |
| abstract_inverted_index.provided | 38 |
| abstract_inverted_index.repeated | 82, 128 |
| abstract_inverted_index.specific | 190 |
| abstract_inverted_index.studies, | 117 |
| abstract_inverted_index.studies. | 171 |
| abstract_inverted_index.valuable | 39 |
| abstract_inverted_index.Occupancy | 78 |
| abstract_inverted_index.conducted | 80, 92 |
| abstract_inverted_index.developed | 133 |
| abstract_inverted_index.estimated | 166 |
| abstract_inverted_index.explored. | 104 |
| abstract_inverted_index.following | 81, 93 |
| abstract_inverted_index.occupancy | 30, 35, 136, 181, 192 |
| abstract_inverted_index.potential | 141 |
| abstract_inverted_index.targeting | 15 |
| abstract_inverted_index.adequately | 103 |
| abstract_inverted_index.assessment | 43 |
| abstract_inverted_index.determined | 31 |
| abstract_inverted_index.engagement | 12 |
| abstract_inverted_index.literature | 185 |
| abstract_inverted_index.mechanisms | 64 |
| abstract_inverted_index.medication | 72 |
| abstract_inverted_index.systematic | 88 |
| abstract_inverted_index.tomography | 2 |
| abstract_inverted_index.differences | 89, 98, 110, 162 |
| abstract_inverted_index.information | 40, 55 |
| abstract_inverted_index.side-effect | 68 |
| abstract_inverted_index.development. | 53 |
| abstract_inverted_index.hypothesised | 107 |
| abstract_inverted_index.implications | 175 |
| abstract_inverted_index.medications. | 16 |
| abstract_inverted_index.relationship | 18, 188 |
| abstract_inverted_index.upregulation | 157 |
| abstract_inverted_index.accumulation. | 130 |
| abstract_inverted_index.administered) | 27 |
| abstract_inverted_index.concentration | 23 |
| abstract_inverted_index.indispensable | 6 |
| abstract_inverted_index.tolerability. | 198 |
| abstract_inverted_index.understanding | 61 |
| abstract_inverted_index.interpretation | 178 |
| abstract_inverted_index.parsimoniously | 159 |
| abstract_inverted_index.quantification | 9 |
| abstract_inverted_index.pharmaceuticals | 46 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 95 |
| corresponding_author_ids | https://openalex.org/A5005098704 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 2 |
| corresponding_institution_ids | https://openalex.org/I4210093835 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8100000023841858 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.67635677 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |