89 Zr-3,2-HOPO-Mesothelin Antibody PET Imaging Reflects Tumor Uptake of Mesothelin-Targeted 227 Th-Conjugate Therapy in Mice.

Autor: Broer LN; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Knapen DG; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Suurs FV; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Moen I; Bayer AS, Oslo, Norway., Giesen D; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Waaijer SJH; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Indrevoll B; Bayer AS, Oslo, Norway., Ellingsen C; Bayer AS, Oslo, Norway., Kristian A; Bayer AS, Oslo, Norway., Cuthbertson AS; Bayer AS, Oslo, Norway., de Groot DA; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Cole PE; Bayer U.S., LLC, Whippany, New Jersey., de Vries EGE; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Hagemann UB; Bayer AG, Berlin, Germany., Lub-de Hooge MN; Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and m.n.de.hooge@umcg.nl.; Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Jazyk: angličtina
Zdroj: Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2022 Nov; Vol. 63 (11), pp. 1715-1721. Date of Electronic Publication: 2022 Apr 14.
DOI: 10.2967/jnumed.121.263079
Abstrakt: The mesothelin (MSLN)-targeted 227 Th conjugate is a novel α-therapy developed to treat MSLN-overexpressing cancers. We radiolabeled the same antibody-chelator conjugate with 89 Zr to evaluate whether PET imaging with 89 Zr-MSLN matches 227 Th-MSLN tumor uptake, biodistribution, and antitumor activity. Methods: Serial PET imaging with protein doses of 4, 20, or 40 μg of 89 Zr-MSLN and 89 Zr-control was performed up to 168 h after tracer injection in human tumor-bearing nude mice with high (HT29-MSLN) and low (BxPc3) MSLN expression. 89 Zr-MSLN and 227 Th-MSLN ex vivo tumor uptake and biodistribution were compared at 6 time points in HT29-MSLN and in medium-MSLN-expressing (OVCAR-3) tumor-bearing mice. 89 Zr-MSLN PET imaging was performed before 227 Th-MSLN treatment in HT29-MSLN and BxPc3 tumor-bearing mice. Results: 89 Zr-MSLN PET imaging showed an SUV mean of 2.2 ± 0.5 in HT29-MSLN tumors. Ex vivo tumor uptake was 10.6% ± 2.4% injected dose per gram at 168 h. 89 Zr-MSLN tumor uptake was higher than uptake of 89 Zr-control ( P = 0.0043). 89 Zr-MSLN and 227 Th-MSLN showed comparable tumor uptake and biodistribution in OVCAR-3 and HT29-MSLN tumor-bearing mice. Pretreatment SUV mean was 2.2 ± 0.2 in HT29-MSLN tumors, which decreased in volume on 227 Th-MSLN treatment. BxPc3 tumors showed an SUV mean of 1.2 ± 0.3 and remained similar in size after 227 Th-MSLN treatment. Conclusion: 89 Zr-MSLN PET imaging reflected MSLN expression and matched 227 Th-MSLN tumor uptake and biodistribution. Our data support the clinical exploration of 89 Zr-MSLN PET imaging together with 227 Th-MSLN therapy, both using the same antibody-chelator conjugate.
(© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)
Databáze: MEDLINE
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