PT  - JOURNAL ARTICLE
AU  - Linda N Broer
AU  - Daan G Knapen
AU  - Frans Valentijn 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 Apr 01
TA  - Journal of Nuclear Medicine
PG  - jnumed.121.263079
4099  - http://jnm.snmjournals.org/content/early/2022/04/14/jnumed.121.263079.short
4100  - http://jnm.snmjournals.org/content/early/2022/04/14/jnumed.121.263079.full
AB  - Rationale: Mesothelin targeted thorium-227 conjugate (227Th-MSLN) is a novel targeted alpha therapy developed to treat mesothelin overexpressing cancers. We radiolabeled the same antibody-chelator conjugate with zirconium-89 (89Zr-MSLN) to evaluate if positron emission tomography (PET) imaging with 89Zr-MSLN matches with 227Th-MSLN tumor uptake, biodistribution, and antitumor activity. Experimental design: Serial PET imaging with protein doses of 4, 20, or 40 μg 89Zr-MSLN and 89Zr-control was performed up to 168 h post tracer injection (pi) in high (HT29-MSLN) and low (BxPc3) mesothelin expressing human tumor-bearing nude mice. 89Zr-MSLN and 227Th-MSLN ex vivo tumor uptake and biodistribution were compared at 6 time-points in HT29-MSLN and in medium mesothelin 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 mean standardized uptake value (SUVmean) in HT29-MSLN tumors of 2.2 ± 0.5. Ex vivo tumor uptake was 10.6% ± 2.4% injected dose per gram (%ID/g) 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. SUVmean was 1.8-fold higher in HT29-MSLN than in BxPc3 tumors, matching with stronger 227Th-MSLN antitumor activity. Conclusion: 89Zr-MSLN PET imaging reflected mesothelin expression and matched with 227Th-MSLN tumor uptake, biodistribution, and antitumor activity. Our data support the clinical exploration of 89Zr-MSLN PET imaging together with 227Th-MSLN therapy, both using the same antibody-chelator conjugate.