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CXCR4-Directed Imaging and Endoradiotherapy in Desmoplastic Small Round Cell Tumors.

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Author information

Affiliations

  • 1. Department of Internal Medicine II, Medical Oncology and Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Würzburg, Germany.
      Authors
    • Hartlapp I 1
    • Weich A 1
    • Rasche L 1
    • Einsele H 1
    • Kunzmann V 1
    (5 authors)
  • 2. Department of Nuclear Medicine and Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Würzburg, Germany.
      Authors
    • Hartrampf PE 2
    • Serfling SE 2
    • Hänscheid H 2
    • Schirbel A 2
    • Werner RA 2
    • Buck AK 2
    (6 authors)
  • 3. Department of Pathology and Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany.
      Authors
    • Wild V 3
    • Roth S 3
    • Rosenwald A 3
    (3 authors)
  • 4. Department of Diagnostic and Interventional Radiology and Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Würzburg, Germany.
      Authors
    • Mihatsch PW 4
    (1 author)
  • 5. Department of General, Visceral, Transplantation, Vascular, and Pediatric Surgery and Comprehensive Cancer Center Mainfranken Würzburg, University Hospital Würzburg, Würzburg, Germany.
      Authors
    • Hendricks A 5
    • Wiegering A 5
    (2 authors)
    • Show all (9)

ORCIDs linked to this article

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine, 22 Jun 2023, 64(9):1424-1430
https://doi.org/10.2967/jnumed.123.265464 PMID: 37348915 

Abstract 

Desmoplastic small round cell tumor (DSRCT) is a rare, radiosensitive, yet difficult-to-treat sarcoma subtype affecting predominantly male adolescents. Extensive intraperitoneal seeding is common and requires multimodal management. With no standard therapy established, the prognosis remains poor, and new treatment options are needed. We demonstrate the clinical potential of C-X-C motif chemokine receptor 4 (CXCR4)-directed imaging and endoradiotherapy in DSRCT. Methods: Eight male patients underwent dual-tracer imaging with [18F]FDG and CXCR4-directed [68Ga]pentixafor PET/CT. A visual comparison of both tracers, along with uptake quantification in active DSRCT lesions, was performed. [68Ga]pentixafor uptake was correlated with immunohistochemical CXCR4 expression on tumor cells. Four patients with end-stage progressive disease underwent CXCR4-based endoradiotherapy. We report the safety, response by RECIST 1.1, and survival after endoradiotherapy. Results: Uptake of [68Ga]pentixafor in tumor lesions was demonstrated in all patients with DSRCT, providing diagnostic power comparable to [18F]FDG PET. Corresponding CXCR4 expression was confirmed by immunohistochemistry in all DSRCT biopsies. Finally, 4 patients were treated with CXCR4-directed [90Y]endoradiotherapy, 3 in a myeloablative dose range with subsequent autologous stem cell transplantation. All 3 required transfusions, and febrile neutropenia occurred in 2 patients (resulting in 1 death). Notably, severe nonhematologic adverse events were absent. We observed signs of response in all 3 patients, translating into disease stabilization in 2 patients for 143 and 176 d, respectively. In the third patient, postmortem autopsy confirmed a partial pathologic response. Conclusion: We validated CXCR4 as a diagnostic biomarker and a promising target for endoradiotherapy in DSRCT, demonstrated its feasibility, and provided the first evidence of its clinical efficacy.

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