RT Journal Article
SR Electronic
T1 CXCR4-Directed Imaging and Endoradiotherapy in Desmoplastic Small Round Cell Tumors
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1424
OP 1430
DO 10.2967/jnumed.123.265464
VO 64
IS 9
A1 Hartlapp, Ingo
A1 Hartrampf, Philipp E.
A1 Serfling, Sebastian E.
A1 Wild, Vanessa
A1 Weich, Alexander
A1 Rasche, Leo
A1 Roth, Sabine
A1 Rosenwald, Andreas
A1 Mihatsch, Patrick W.
A1 Hendricks, Anne
A1 Wiegering, Armin
A1 Wiegering, Verena
A1 Hänscheid, Heribert
A1 Schirbel, Andreas
A1 Werner, Rudolf A.
A1 Buck, Andreas K.
A1 Wester, Hans-Jürgen
A1 Einsele, Hermann
A1 Kunzmann, Volker
A1 Lapa, Constantin
A1 Kortüm, K. Martin
YR 2023
UL http://jnm.snmjournals.org/content/64/9/1424.abstract
AB 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.