Evidence map›Paper›PMID 42014564›Full record

ArticleJournal of pharmacokinetics and pharmacodynamics2026

Tracer kinetic modeling of a 14 kDa anti-CD8 PET tracer (2C8v144) for in vivo estimation of CD8 expression in tissue and blood, binding affinity, and total body receptor occupancy.

Ruediger E Port, C Andrew Boswell, Annie Ogasawara, Herman Gill, Jan Marik, Alice F Tarantal, Eric Berg, Simon P Williams, Gregory Z Ferl

Erratum issuedAbstract read
In one paragraph

Article in Journal of pharmacokinetics and pharmacodynamics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Ruediger E PortDepartment of Preclinical and Translational PKPD, Genentech, Inc., South San Francisco, CA, USA. ruediger.port@gmail.com.
C Andrew BoswellDepartment of Preclinical and Translational PKPD, Genentech, Inc., South San Francisco, CA, USA.
Annie OgasawaraDepartment of Translational Imaging, Genentech, Inc., South San Francisco, CA, USA.
Herman GillDepartment of Translational Imaging, Genentech, Inc., South San Francisco, CA, USA.
Jan MarikDepartment of Translational Imaging, Genentech, Inc., South San Francisco, CA, USA.
Alice F TarantalDepartment of Pediatrics and Department of Cell Biology and Human Anatomy, School of Medicine, and California National Primate Research Center, University of California Davis, Davis, CA, USA.
Eric BergDepartment of Biomedical Engineering, University of California Davis, Davis, CA, USA.
Simon P WilliamsDepartment of Translational Imaging, Genentech, Inc., South San Francisco, CA, USA.
Gregory Z FerlDepartment of Preclinical and Translational PKPD, Genentech, Inc., South San Francisco, CA, USA. gzferl@gmail.com.

Funding

National Institute on Aging (NIA) ColonyP51OD011107 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Simon J. Atkinson · 2012 to 2026
$191.5M
Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI KC KENT LLOYD · 2002 to 2026
$84.9M
Validated Immunoassays to Accelerate Therapeutic Genome Editing INDsU01AI191209 · NIAID · UNIVERSITY OF CALIFORNIA AT DAVIS · PI DENNIS J. HARTIGAN-O'CONNOR, Alice F Tarantal · 2025 to 2026
$2.1M
PET/CT for Nonhuman Primate ImagingS10RR025063 · NCRR · UNIVERSITY OF CALIFORNIA AT DAVIS · PI TARANTAL, ALICE F · 2011 to 2011
$2.1M
miniEXPLORER-II for Total-Body PET Translational ImagingS10OD028713 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI TARANTAL, ALICE F · 2020 to 2020
$1.9M
California National Primate Research Center OD-011107NCI NIH HHS P30 CA093373NCRR NIH HHS S10 RR025063NIAID NIH HHS U01 AI191209NIH HHS P51 OD011107NIH HHS RR-025063; AFTNIH HHS S10 OD028713
6 · The paper itself

Abstract

We are developing a 14.3 kDa anti-CD8 VHH tracer, [[Formula: see text]F]-2C8v144 (binding tracer, B), along with a nonbinding control tracer, [[Formula: see text]F]-2C8v145 (C), in order to track CD8+ (“cytotoxic”) T cells in malignant tumors during immunotherapy by Positron Emission Tomography (PET). Arterial blood concentrations of C and B were monitored in three rhesus monkeys upon i.v. injection of mass doses/kg varying approximately 5–fold for both tracers. Plasma concentrations, calculated from individual hematocrit measurements assuming no cellular uptake, were analyzed by mixed–effects compartmental modeling, by assuming the parameters of non-specific distribution and elimination (estimated based on the PET-based arterial blood concentrations) to be the same for B as for C. C exhibited linear three–compartment kinetics with a mean residence time of 26 min. Nonlinear kinetics of B suggesting saturable, reversible binding outside of circulating blood were described by an average association rate constant, [Formula: see text], and an equilibrium dissociation constant, [Formula: see text]. Binding in blood to circulating CD8+ cells was described by a different association rate constant, [Formula: see text], and the same [Formula: see text]. The total body content of CD8 receptors was estimated at 1.7 nmol/kg body weight, with 2.7% of the total present in blood. The estimate of [Formula: see text], 0.0097/(min·nM), was > 50–fold lower than [Formula: see text] determined in vitro by Surface Plasmon Resonance (SPR, 0.50/(min·nM), yet the estimated [Formula: see text], 0.23 nM, was similar to the SPR estimate (0.13 nM) suggesting that the model informs about affinity. The model also yields predicted total body receptor occupancies and plasma concentrations of unbound B, i.e. the arterial input function needed for analyzing tracer kinetics in malignant tumors.

Indexed as

CD8 AntigensCD8-Positive T-LymphocytesPositron-Emission TomographyAnimalsKineticsMacaca mulattaProtein BindingTissue DistributionCD8 AntigensCD8Cytotoxic T-cells[[Formula: see text]F]-2C8v144[[Formula: see text]F]-2C8v145PETPlasma kineticsRhesus monkeys

Identifiers

PMID42014564
PMCPMC13503381

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.