RT Journal Article
SR Electronic
T1 <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
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1715
OP 1721
DO 10.2967/jnumed.121.263079
VO 63
IS 11
A1 Broer, Linda N.
A1 Knapen, Daan G.
A1 Suurs, Frans V.
A1 Moen, Ingrid
A1 Giesen, Danique
A1 Waaijer, Stijn J.H.
A1 Indrevoll, Baard
A1 Ellingsen, Christine
A1 Kristian, Alexander
A1 Cuthbertson, Alan S.
A1 de Groot, Derk-Jan A.
A1 Cole, Patricia E.
A1 de Vries, Elisabeth G.E.
A1 Hagemann, Urs B.
A1 Lub-de Hooge, Marjolijn N.
YR 2022
UL http://jnm.snmjournals.org/content/63/11/1715.abstract
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.