A New Diagnostic Algorithm to Non-invasively Track Fibrotic Changes in Myeloproliferative Neoplasms Based on C-C Chemokine Receptor 2 Detection. From Flow Cytometry to the Development of Targeted Positron Emission Tomography Molecular Imaging. Pre-clinical Studies and First In-human Proof of Concept
Key claim: CCR2-expressing cells detectable via flow cytometry and 68Ga-DOTA-ECL1i PET-CT imaging may enable non-invasive, early identification and tracking of bone marrow fibrosis in myeloproliferative neoplasms.
Abstract
Chronic “Philadelphia-negative” myeloproliferative syndromes are chronic blood disorders. They include essential thrombocythemia, polycythemia vera, and myelofibrosis. Myelofibrosis may arise de novo (“primary myelofibrosis”) or represent the evolution of essential thrombocythemia or polycythemia vera (“secondary myelofibrosis”).
The myelofibrotic stage-characterized, as the name implies, by the presence of bone marrow fibrosis (deposition of scar-like tissue)-is generally associated with a more severe and symptomatic disease. To date, the only way to assess fibrotic progression in these disorders is bone marrow biopsy.
The aim of this project is to evaluate whether the identification, tracking, and quantification of cells expressing a specific receptor (CCR2), a selective biomarker of fibrosis, may allow early and non-invasive identification of the fibrotic stage of the disease through:
- laboratory analysis on a blood sample (using flow cytometry)
- use in PET-CT (positron emission tomography combined with computed tomography) of a tracer specific for the CCR2 receptor, capable of selectively binding to CCR2-expressing cells (⁶⁸Ga-DOTA-ECL1i).
Why this matters
Bone marrow fibrosis assessment currently depends on invasive biopsy, limiting both early detection of fibrotic transformation in ET/PV and longitudinal tracking of fibrosis dynamics in PMF. A CCR2-targeted diagnostic combining flow cytometry with 68Ga-DOTA-ECL1i PET-CT could provide a subtype-spanning, non-invasive readout of fibrotic activity, complementing emerging modalities like pSWE and potentially reshaping how transformation risk and treatment-induced fibrosis regression are monitored across MPN subtypes.