ArticleMolecular pharmaceutics2026
Development of [111In]In-CHX-A″-DTPA-αCD68 for ImmunoSPECT to Image Murine Macrophages.
Article in Molecular pharmaceutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- A FABulous approach to image human macrophages.European journal of nuclear medicine and molecular imaging · 2026Article
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Abstract
purposeHigh tumor-associated macrophage (TAM) abundance is associated with poorer prognoses across many cancers, including renal cell carcinoma (RCC). CD68 is an established clinical biomarker for macrophages in patient tissues and is also expressed in mouse macrophages, making it an attractive target for bridging preclinical and clinical imaging of macrophages. We developed an anti-mouse CD68 (mCD68) immunoSPECT imaging agent to noninvasively quantify TAM burden in vivo and evaluate response to macrophage-modulating treatment in a syngeneic RCC tumor model.
methods[111In]In-CHX-A″-DTPA-αCD68 was synthesized by optimizing chelator conjugation and radiolabeling conditions, then characterized for binding affinity, stability, and specificity by in vitro assays. In vivo specificity was assessed in the Renca syngeneic RCC model by comparing biodistribution of [111In]In-CHX-A″-DTPA-αCD68 with that of the radiolabeled IgG isotype control. ImmunoSPECT signal was correlated with ex vivo CD68 expression measured by flow cytometry of dissociated tumors and spleens. To evaluate response to macrophage-modulating treatment, a 2 × 2 factorial study was conducted in which Renca-allografted mice received either anti-CSF1R or IgG control, followed by immunoSPECT imaging with [111In]In-CHX-A″-DTPA-αCD68 or radiolabeled isotype control; organ-to-heart SUVR was correlated with ex vivo CD68 expression by flow cytometry.
results[111In]In-CHX-A″-DTPA-αCD68 bound specifically to CD68 in bone marrow-derived macrophages, with high binding affinity (KD = 7.99 ± 2.26 nM) to the CD68 protein. In Renca-allografted mice, immunoSPECT signal correlated strongly with ex vivo CD68 expression measured by flow cytometry of dissociated tumor and spleen cells (r = 0.854). Biodistribution studies confirmed specific uptake in vivo, with 2-fold, 8-fold, and 8-fold greater uptake in tumor, spleen, and bone marrow, respectively, compared with the radiolabeled isotype control. Treatment with the macrophage-depleting anti-CSF1R resulted in ∼40% lower tumor-to-heart SUVR with [111In]In-CHX-A″-DTPA-αCD68 compared with the isotype control, despite no change in tumor volumes. ImmunoSPECT signal remained strongly correlated with ex vivo CD68 expression measured by flow cytometry (r = 0.952).
conclusionsThis study demonstrates the first example of immunoSPECT imaging of CD68 in vivo. ImmunoSPECT imaging of CD68 provides a direct, noninvasive measure of total TAM burden in RCC and represents a translatable approach for monitoring response to macrophage-modulating treatments in preclinical studies.
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