PT  - JOURNAL ARTICLE
AU  - Linda N. Broer
AU  - Daan G. Knapen
AU  - Frans V. Suurs
AU  - Ingrid Moen
AU  - Danique Giesen
AU  - Stijn J.H. Waaijer
AU  - Baard Indrevoll
AU  - Christine Ellingsen
AU  - Alexander Kristian
AU  - Alan S. Cuthbertson
AU  - Derk-Jan A. de Groot
AU  - Patricia E. Cole
AU  - Elisabeth G.E. de Vries
AU  - Urs B. Hagemann
AU  - Marjolijn N. Lub-de Hooge
TI  - <sup>89</sup>Zr-3,2-HOPO-Mesothelin Antibody PET Imaging Reflects Tumor Uptake of Mesothelin-Targeted <sup>227</sup>Th-Conjugate Therapy in Mice
AID  - 10.2967/jnumed.121.263079
DP  - 2022 Nov 01
TA  - Journal of Nuclear Medicine
PG  - 1715--1721
VI  - 63
IP  - 11
4099  - http://jnm.snmjournals.org/content/63/11/1715.short
4100  - http://jnm.snmjournals.org/content/63/11/1715.full
SO  - J Nucl Med2022 Nov 01; 63
AB  - The mesothelin (MSLN)-targeted 227Th conjugate is a novel α-therapy developed to treat MSLN-overexpressing cancers. We radiolabeled the same antibody–chelator conjugate with 89Zr to evaluate whether PET imaging with 89Zr-MSLN matches 227Th-MSLN tumor uptake, biodistribution, and antitumor activity. Methods: Serial PET imaging with protein doses of 4, 20, or 40 μg of 89Zr-MSLN and 89Zr-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. 89Zr-MSLN and 227Th-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. 89Zr-MSLN PET imaging was performed before 227Th-MSLN treatment in HT29-MSLN and BxPc3 tumor–bearing mice. Results: 89Zr-MSLN PET imaging showed an SUVmean 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. 89Zr-MSLN tumor uptake was higher than uptake of 89Zr-control (P = 0.0043). 89Zr-MSLN and 227Th-MSLN showed comparable tumor uptake and biodistribution in OVCAR-3 and HT29-MSLN tumor–bearing mice. Pretreatment SUVmean was 2.2 ± 0.2 in HT29-MSLN tumors, which decreased in volume on 227Th-MSLN treatment. BxPc3 tumors showed an SUVmean of 1.2 ± 0.3 and remained similar in size after 227Th-MSLN treatment. Conclusion: 89Zr-MSLN PET imaging reflected MSLN expression and matched 227Th-MSLN tumor uptake and biodistribution. Our data support the clinical exploration of 89Zr-MSLN PET imaging together with 227Th-MSLN therapy, both using the same antibody–chelator conjugate.