The tracer at the center of the study, known as [68Ga]Ga-ATH001, is an Affibody molecule, a small engineered protein scaffold roughly a tenth the size of an antibody, that binds with picomolar affinity to platelet-derived growth factor receptor beta, or PDGFRβ. This receptor is a well-established hallmark of activated pericytes and, critically, of activated hepatic stellate cells, the liver-resident cells that transform into collagen-producing factories during fibrogenesis. Because PDGFRβ is upregulated on the cells actively driving extracellular matrix deposition across the liver, lung, heart and tumor stroma, it offers a molecular handle for imaging not the aftermath of scarring but the scarring process itself, while it is still underway and still treatable.

Before any new radiotracer can be used diagnostically, regulators and clinicians need to know exactly where it goes in the body and how much radiation it deposits along the way. That is the question the research team, led by Mark Lubberink of Uppsala University together with colleagues from Karolinska Institutet, Antaros Medical, Antaros Tracer and Takeda Development Center Americas, set out to answer in a first-in-human study registered as NCT06562361. The dosimetry cohort comprised six participants: three healthy volunteers, all 22 years old, and three patients with metabolic dysfunction-associated steatohepatitis, or MASH, the aggressive form of fatty liver disease in which fibrosis is a central driver of disease progression and mortality.

Each participant received an intravenous bolus of approximately 2.5 megabecquerels per kilogram of body weight of the gallium-68-labeled tracer, corresponding to an average injected activity of 178 MBq and a peptide mass of just 51 micrograms, roughly a thousandth of a drop of protein. Imaging began immediately, with a dynamic PET/MRI scan over the abdomen capturing the first 35 minutes of tracer distribution in real time, followed by whole-body PET scans at one, two and three hours after injection. In total, 25 organs and tissues were segmented and analyzed, from the liver, kidneys and spleen to the red bone marrow, salivary glands, thyroid and gonads, providing an unusually comprehensive map of the tracer’s journey through the body.

The biodistribution results told a clean and encouraging story. The tracer spread rapidly through the circulation and then cleared quickly from most tissues, so that by two hours after injection, radioactivity remained essentially only in the kidneys and bladder, the sole route of excretion, and in the spleen, which naturally expresses abundant PDGFRβ. In the healthy volunteers, liver uptake had already fallen close to background levels. In the MASH patients, by contrast, liver uptake was significantly higher, with a standardized uptake value of 4.0 compared with 2.8 in the healthy group, a difference the authors attribute to the upregulation of PDGFRβ on activated hepatic stellate cells engaged in ongoing fibrogenesis. In other words, the tracer did exactly what it was designed to do: distinguish fibrotically active livers from quiescent ones.

On the radiation side, the calculations, performed with the IDAC DOSE 2.1 software using the ICRP 103 framework and ICRP 110 reference phantoms scaled to each participant’s body weight, yielded a sex-averaged effective dose of 0.028 ± 0.002 millisieverts per megabecquerel. The kidneys emerged as the dose-limiting organ, absorbing 0.34 mGy/MBq in males and 0.46 mGy/MBq in females, a consequence of the renal tubules reabsorbing the peptide-based tracer and trapping the gallium-68 intracellularly, a well-known behavior of this class of small radiolabeled proteins. At the clinically targeted activity of 2 MBq per kilogram, roughly 150 MBq for a typical adult male, the total effective dose would come to 4.1 mSv, with kidney absorbed doses of about 50 mGy in males and 55 mGy in females.

Those numbers place [68Ga]Ga-ATH001 in familiar company. Its effective dose is comparable to other gallium-68-labeled Affibody molecules previously evaluated in humans and only slightly higher than that of established peptide tracers such as [68Ga]Ga-DOTATOC, used routinely in neuroendocrine tumor imaging, or the workhorse PET radiopharmaceutical fluorodeoxyglucose. Given that a single abdominal CT scan can deliver an effective dose in the range of 10 mSv, a 4.1 mSv PET study that can be repeated over months or years represents a radiation profile compatible with the longitudinal study designs that fibrosis research desperately needs, subject of course to applicable regulatory and ethical requirements.

Safety was equally reassuring. Participants were monitored for up to 24 hours after dosing with laboratory assessments, vital signs and electrocardiography, and none experienced any adverse effects following administration of up to 70 micrograms of the precursor peptide, approximately 0.9 micrograms per kilogram. The authors also carefully catalogued the uncertainties in their dosimetry, noting that the scan protocol, with its 35-minute dynamic acquisition followed by serial whole-body imaging, kept the extrapolated fraction of the time-integrated activity below 20 percent for most organs in the dynamic field of view, and that the bladder dose estimate, based solely on PET data without assuming voiding, likely overestimates the true absorbed dose.

The significance of this work extends well beyond liver disease. Because PDGFRβ activity is entwined with angiogenesis, tissue remodeling and wound healing throughout the body, a validated PET marker of the receptor opens the door to non-invasive monitoring of fibrogenesis in the lung, the heart, where a separate trial in myocardial infarction patients is already underway, and the tumor microenvironment. For MASH in particular, where novel anti-fibrotic drugs are flooding the pipeline and patient stratification remains a major bottleneck, a tracer that quantifies active fibrogenesis could transform how patients are selected for trials and how treatment response is measured, replacing repeated biopsies with a one-hour scan.

Much work remains before [68Ga]Ga-ATH001 reaches routine clinical use. The dosimetry cohort was small, and liver uptake will be explored further in additional participants across different stages of MASH within the ongoing clinical study. Still, the combination of favorable dosimetry, clean safety data and demonstrable discrimination between healthy and fibrotically active livers gives the tracer a strong foundation for the next phase of development. If subsequent studies confirm its diagnostic accuracy, clinicians may soon gain what they have lacked for decades: a repeatable, quantitative window into the scarring process itself, caught early enough to do something about it.

Subject of Research: First-in-human biodistribution and radiation dosimetry of the PDGFRβ-targeting PET tracer [68Ga]Ga-ATH001 for imaging active fibrosis

Article Title: Biodistribution and radiation dosimetry of the PDGFRβ targeting PET tracer [68Ga]Ga-ATH001

Article References: Lubberink, M., Lohith, T. G., Derdak, Z., Wilkens, P., Palmér, E., Ramolli, A., Ferrat, M., Tran, T. A., Mitran, B., Abouyzayed, A., Johansson, L., Wennbo, H., Rorsman, F., Vessby, J., & Eriksson, O. (2026). Biodistribution and radiation dosimetry of the PDGFRβ targeting PET tracer [68Ga]Ga-ATH001. European Journal of Nuclear Medicine and Molecular Imaging. https://doi.org/10.1007/s00259-026-08167-9

Image Credits: AI Generated

DOI: 10.1007/s00259-026-08167-9

Keywords: PET imaging, PDGFRβ, fibrosis, radiation dosimetry, Affibody molecule, gallium-68, MASH, liver fibrogenesis, hepatic stellate cells, first-in-human study, molecular imaging, radiotracer safety