Noninvasive Monitoring of Inflammatory Processes by Myeloid Cell–Directed PET Tracers in an Experimental Severe Acute Respiratory Syndrome Coronavirus 2 Infection Model

Sep 29, 2026

Noninvasive PET imaging was developed to monitor inflammatory dynamics driven by myeloid cells during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A camelid-derived single-domain antibody recognizing human signal-regulatory protein-α (SIRPα) was radiolabeled with 64Cu to create [64Cu]Cu-SIRPα-nanobody and validated in nonhuman primates. Six cynomolgus macaques underwent baseline and longitudinal PET/CT alongside viral RNA, CT lesion assessment, blood counts, and cytokine mediator monitoring, with TSPO tracer comparison in subsets. [64Cu]Cu-SIRPα-nanobody revealed time-dependent accumulation in lymph nodes, spleen, and bone marrow.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Methods

PET/CT tracer preparation and validation

Animal infection and imaging schedule

Biomarker collection and outcome measures

Results

Viral confirmation and lesion detection

Tracer uptake patterns and comparisons

Conclusion

Noninvasive Monitoring of Inflammatory Processes by Myeloid Cell–Directed PET Tracers in an Experimental Severe Acute Respiratory Syndrome Coronavirus 2 Infection Model Marieke A. Stammes 1, Gerrit Koopman 1, Teresa R. Wagner2, Bjoern Traenkle2, Philipp D. Kaiser2, Petra Mooij1, Nicole van der Werff1, Roja Fidel Acar 1, Kinga P. Bszrmnyi1, Simone Blaess2,3, Stefania Pezzana3, Gerald Reischl3,4, Andreas Maurer3,4, Jan A.M. Langermans 1,5, Ulrich Rothbauer4,6, Manfred Kneilling3,4,7, and Dominik Sonanini2,3,4,8 1Biomedical Primate Research Centre, Rijswijk, The Netherlands; 2NMI Natural and Medical Sciences Institute, University of Tu€bingen, Reutlingen, Germany; 3 Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tu€bingen, Eberhard Karls University Tu€bingen, Tu€bingen, Germany; 4Cluster of Excellence iFIT 2180 “Image-Guided and Functionally Instructed Tumor Therapies,” Eberhard Karls University, Tu€bingen, Germany; 5Department of Population Health Sciences, Unit Animals in Science and Society, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands; 6Pharmaceutical Biotechnology, Eberhard Karls University Tu€bingen, Tu€bingen, Germany; 7Department of Dermatology, Eberhard Karls University, Tu€bingen, Germany; and 8Department of Medical Oncology and Pneumology (Internal Medicine VIII), Eberhard Karls University, Tu€bingen, Germany Monitoring the presence and distribution of distinct immune cell populations is key in deciphering immunopathologic disease mechanisms. Considering the crucial role of myeloid cells in provoking hyperinﬂammatory responses associated with coronavirus disease 2019, a camelid-derived single-domain antibody speciﬁcally recognizing human signal-regulatory protein-a (SIRPa) as a biomarker for myeloid cells has been generated and radiolabeled with 64Cu, that is,[64Cu]copper-SIRPa-nanobody ([64Cu]Cu-SIRPa-Nb), for in vivo PET imaging. In this study, this PET tracer was used and validated to monitor the temporal dynamics of inﬂammatory processes during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in nonhuman primates. For further validation, the signal of [64Cu]Cu-SIRPa-Nb was compared with the signal of TSPO-targeting [18F]ﬂuorine-N,Ndiethyl-2-(2-(4-(2-ﬂuoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5a]pyrimidin-3-yl)acetamide([18F]F-DPA714). Methods: Six cynomolgus macaques (Macaca fascicularis) were experimentally infected with SARS-CoV-2 and subsequently monitored for 7 wk. We performed a baseline [64Cu]Cu-SIRPa-Nb PET/CT before infection, followed by repetitive PET/CT on days 3, 10, 24, and 52 after infection covering the head, thorax, and abdominal region. Of the 6 macaques, 3 underwent additional TSPO-targeting [18F]F-DPA714 PET/CT investigations at baseline and at days 2, 9, 23, and 51 after infection. Tracheal and nasal swabs were taken to monitor the course of infection, and changes in blood count and inﬂammatory mediators in the periphery blood were monitored. Results: Detection of subgenomic SARS-CoV-2 messenger RNA from tracheal and nasal swab samples conﬁrmed viral infection of all animals. CT scans identiﬁed initial pulmonary lesions 2 days after infection.[64Cu]Cu-SIRPa-Nb PET/CT revealed increased tracer uptake in themediastinal lymph nodes of all animals, but not in the lung lesions, Received Feb. 14, 2025; revision accepted Jul. 2, 2025 . For correspondence or reprints, contact Marieke Stammes (stammes@ [bprc.nl](bprc.nl)) or Dominik Sonanini ([dominik.sonanini@med.uni-tuebingen.de](dominik.sonanini@med.uni-tuebingen.de)). Published online Aug. 28, 2025 . Immediate Open Access: Creative Commons Attribution 4.0 International License (CC BY) allows users to share and adapt with attribution, excluding materials credited to previous publications. License: [https://creativecommons](https://creativecommons). org/licenses/by/4.0/. Details: [https://jnm.snmjournals.org/page/permissions](h

FAQs

What PET tracer was used to monitor myeloid-driven inflammation?

A 64Cu-radiolabeled camelid SIRPα single-domain antibody ([64Cu]Cu-SIRPα-nanobody) was used for in vivo PET imaging and monitoring.

How was SARS-CoV-2 infection modeled and monitored over time?

Six cynomolgus macaques were infected with SARS-CoV-2, then repeatedly evaluated for about 7 weeks using longitudinal PET/CT plus swab testing, blood count changes, and inflammatory mediator measurements.

How did the SIRPα tracer performance compare with the TSPO tracer?

[64Cu]Cu-SIRPα-nanobody showed increased uptake with distinct temporal patterns in lymphatic and immune organs, while the TSPO-targeting [18F]F-DPA714 exhibited more homogeneous uptake patterns.

Sep 29, 2026

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