Skip to content
DraconiticResearch
Search Sources API
206,690 studies31 sourcesUpdated 21 min ago
Peer-reviewedCC BY 4.0European Journal of Nuclear Medicine and Molecular Imaging

A FABulous approach to image human macrophages

  • Borna Roohani1,2
  • Ayla Vaughn Embs1
  • Robin Kumar1
  • Supum Lee3,4
  • Samantha R. Katz3
  • Chloe La Prairie5
  • Dajah Nash1
  • Mann Dangarwala1
  • Harriet M. Kluger6
  • Daryl E. Klein7
  • Ping Zhang5
  • Benjamin M. Larimer1
2 more authors
  • Bryce Nelson8
  • Bernadette Marquez-Nostra1
8 affiliations
  1. 1Department of Radiology, University of Alabama at Birmingham, 1824 6th Ave. S., Wallace Tumor Institute 310C, Birmingham, AL 35233 USA
  2. 2Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  3. 3Department of Radiology and Biomedical Imaging, Yale PET Center, Yale University, New Haven, CT USA
  4. 4Medical College of Georgia, Augusta, GA USA
  5. 5Department of Pediatric Dentistry, University of Alabama at Birmingham, Birmingham, AL USA
  6. 6Department of Medicine, Yale University, New Haven, CT USA
  7. 7Department of Pharmacology, Yale University, New Haven, CT USA
  8. 8Orion Pharma, Cambridge, UK
Read full textPDFDOICite

Abstract

Rationale: Imaging tumor-associated macrophages (TAMs) may reflect prognosis, therapeutic response and radiotheranostic potential. We report the discovery and development of a synthetic human Fab as the first immunoPET tracer targeting human CD68 (huCD68), the gold standard histopathological biomarker of pan-macrophages.

Methods: Phage display was used to identify novel huCD68-specific Fabs. The lead Fab for immunoPET development was chosen based on expression yield and stability. Fab was conjugated to p-SCN-Bn-DFO and radiolabeled with 89Zr, yielding [89Zr]Zr-DFO-Fab. Stability and specific binding of the tracer to THP-1 macrophages were assessed in vitro. The specificity of the tracer in vivo was characterized by PET imaging of two different animal models: 1) BALB/c mice bearing huCD68 antigen- or irrelevant protein-plugs, and 2) tumor xenografted NSG mice intratumorally injected with either THP-1 macrophages or THP-1 undifferentiated cells. Finally, tumors were subjected to immunofluorescence (IF) staining of huCD68 and correlated with PET standardized uptake values (SUV).

Results: Four novel huCD68-specific Fabs were identified. Fab8 was chosen as the lead based on high expression yield, purity, and stability. In vivo, [89Zr]Zr-DFO-Fab8 uptake was significantly higher in huCD68 antigen-plugs than in irrelevant protein-plugs at 1- and 4-h post-injection (p.i.). Tracer uptake in THP-1 macrophage tumors was also significantly higher than in THP-1 undifferentiated tumors at 1- and 6-h p.i.. IF of tumors confirmed higher density of huCD68 in those implanted with THP-1 macrophages than those with THP-1 undifferentiated cells. CD68 expression highly correlated with immunoPET SUV.

Conclusion: [89Zr]Zr-DFO-Fab8 binds specifically to huCD68, supporting the feasibility of direct PET-to-histopathogical correlation of total TAM burden.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00259-026-08180-y.

Related

  1. Plasticity of human microglia and brain perivascular macrophages in aging and Alzheimer’s disease
    Donghoon Lee, James M. Vicari, Christian Porras +32
    Nature GeneticsPeer-reviewedLicence not stated29 citedNeurologyOpenAlex
  2. Decreased FSP1 expression under chronic hypoxia sensitizes human macrophages towards ferroptosis
    Anja Wickert, Anna Schwantes, Yara Shadid +3
    Redox BiologyPeer-reviewedCC BYFull textMolecular biology & gene regulationGeneral biologyDOAJ
  3. Brain perivascular macrophages regulate endothelial cell function via a cMAF-dependent transcriptional program in mouse and human
    Simone Brioschi, Julia A. Belk, Steffen E. Storck +39
    CellPeer-reviewedCC BY-NC6 citedNeurologyOpenAlex
  4. TiO2 particles induce CHIT1 and YKL-40 in human macrophages: implications for implant-associated inflammation
    Tatyana N. Sevastyanova, Lina S. Silva-Bermudez, Zhen Jiao +7
    Frontiers in ImmunologyPeer-reviewedCC BY 4.0Surgery & anaesthesiaCrossref
  5. Epithelial to mesenchymal transition and M2 macrophages drive aggressiveness in murine and human sarcomatoid urothelial carcinoma.
    Y. Hayashi, R. Elias, E. Douglass +27
    bioRxivPreprintCC BYFull textOncologybioRxiv

Cite

BibTeXRIS
BibTeX
@article{roohani2026fabulous,
  title = {{A FABulous approach to image human macrophages}},
  author = {Borna Roohani and Ayla Vaughn Embs and Robin Kumar and Supum Lee and Samantha R. Katz and Chloe La Prairie and Dajah Nash and Mann Dangarwala and Harriet M. Kluger and Daryl E. Klein and Ping Zhang and Benjamin M. Larimer and Bryce Nelson and Bernadette Marquez-Nostra},
  journal = {European Journal of Nuclear Medicine and Molecular Imaging},
  year = {2026},
  month = sep,
  doi = {10.1007/s00259-026-08180-y},
  url = {https://doi.org/10.1007/s00259-026-08180-y},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - A FABulous approach to image human macrophages
AU  - Borna Roohani
AU  - Ayla Vaughn Embs
AU  - Robin Kumar
AU  - Supum Lee
AU  - Samantha R. Katz
AU  - Chloe La Prairie
AU  - Dajah Nash
AU  - Mann Dangarwala
AU  - Harriet M. Kluger
AU  - Daryl E. Klein
AU  - Ping Zhang
AU  - Benjamin M. Larimer
AU  - Bryce Nelson
AU  - Bernadette Marquez-Nostra
PY  - 2026
DA  - 2026/09/28
JO  - European Journal of Nuclear Medicine and Molecular Imaging
DO  - 10.1007/s00259-026-08180-y
UR  - https://doi.org/10.1007/s00259-026-08180-y
AB  - Rationale: Imaging tumor-associated macrophages (TAMs) may reflect prognosis, therapeutic response and radiotheranostic potential. We report the discovery and development of a synthetic human Fab as the first immunoPET tracer targeting human CD68 (huCD68), the gold standard histopathological biomarker of pan-macrophages.  Methods: Phage display was used to identify novel huCD68-specific Fabs. The lead Fab for immunoPET development was chosen based on expression yield and stability. Fab was conjugated to p-SCN-Bn-DFO and radiolabeled with 89Zr, yielding [89Zr]Zr-DFO-Fab. Stability and specific binding of the tracer to THP-1 macrophages were assessed in vitro. The specificity of the tracer in vivo was characterized by PET imaging of two different animal models: 1) BALB/c mice bearing huCD68 antigen- or irrelevant protein-plugs, and 2) tumor xenografted NSG mice intratumorally injected with either THP-1 macrophages or THP-1 undifferentiated cells. Finally, tumors were subjected to immunofluorescence (IF) staining of huCD68 and correlated with PET standardized uptake values (SUV).  Results: Four novel huCD68-specific Fabs were identified. Fab8 was chosen as the lead based on high expression yield, purity, and stability. In vivo, [89Zr]Zr-DFO-Fab8 uptake was significantly higher in huCD68 antigen-plugs than in irrelevant protein-plugs at 1- and 4-h post-injection (p.i.). Tracer uptake in THP-1 macrophage tumors was also significantly higher than in THP-1 undifferentiated tumors at 1- and 6-h p.i.. IF of tumors confirmed higher density of huCD68 in those implanted with THP-1 macrophages than those with THP-1 undifferentiated cells. CD68 expression highly correlated with immunoPET SUV.  Conclusion: [89Zr]Zr-DFO-Fab8 binds specifically to huCD68, supporting the feasibility of direct PET-to-histopathogical correlation of total TAM burden.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00259-026-08180-y.
SN  - 1619-7070
SN  - 1619-7089
ER  -