89 Zr-3,2-HOPO-Mesothelin Antibody PET Imaging Reflects Tumor Uptake of Mesothelin-Targeted 227 Th-Conjugate Therapy in Mice
The mesothelin (MSLN)-targeted Th conjugate is a novel α-therapy developed to treat MSLN-overexpressing cancers. We radiolabeled the same antibody-chelator conjugate with Zr to evaluate whether PET imaging with Zr-MSLN matches Th-MSLN tumor uptake, biodistribution, and antitumor activity. Serial PET...
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Published in | The Journal of nuclear medicine (1978) Vol. 63; no. 11; p. 1715 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.11.2022
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Abstract | The mesothelin (MSLN)-targeted
Th conjugate is a novel α-therapy developed to treat MSLN-overexpressing cancers. We radiolabeled the same antibody-chelator conjugate with
Zr to evaluate whether PET imaging with
Zr-MSLN matches
Th-MSLN tumor uptake, biodistribution, and antitumor activity.
Serial PET imaging with protein doses of 4, 20, or 40 μg of
Zr-MSLN and
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.
Zr-MSLN and
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.
Zr-MSLN PET imaging was performed before
Th-MSLN treatment in HT29-MSLN and BxPc3 tumor-bearing mice.
Zr-MSLN PET imaging showed an SUV
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.
Zr-MSLN tumor uptake was higher than uptake of
Zr-control (
= 0.0043).
Zr-MSLN and
Th-MSLN showed comparable tumor uptake and biodistribution in OVCAR-3 and HT29-MSLN tumor-bearing mice. Pretreatment SUV
was 2.2 ± 0.2 in HT29-MSLN tumors, which decreased in volume on
Th-MSLN treatment. BxPc3 tumors showed an SUV
of 1.2 ± 0.3 and remained similar in size after
Th-MSLN treatment.
Zr-MSLN PET imaging reflected MSLN expression and matched
Th-MSLN tumor uptake and biodistribution. Our data support the clinical exploration of
Zr-MSLN PET imaging together with
Th-MSLN therapy, both using the same antibody-chelator conjugate. |
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AbstractList | The mesothelin (MSLN)-targeted
Th conjugate is a novel α-therapy developed to treat MSLN-overexpressing cancers. We radiolabeled the same antibody-chelator conjugate with
Zr to evaluate whether PET imaging with
Zr-MSLN matches
Th-MSLN tumor uptake, biodistribution, and antitumor activity.
Serial PET imaging with protein doses of 4, 20, or 40 μg of
Zr-MSLN and
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.
Zr-MSLN and
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.
Zr-MSLN PET imaging was performed before
Th-MSLN treatment in HT29-MSLN and BxPc3 tumor-bearing mice.
Zr-MSLN PET imaging showed an SUV
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.
Zr-MSLN tumor uptake was higher than uptake of
Zr-control (
= 0.0043).
Zr-MSLN and
Th-MSLN showed comparable tumor uptake and biodistribution in OVCAR-3 and HT29-MSLN tumor-bearing mice. Pretreatment SUV
was 2.2 ± 0.2 in HT29-MSLN tumors, which decreased in volume on
Th-MSLN treatment. BxPc3 tumors showed an SUV
of 1.2 ± 0.3 and remained similar in size after
Th-MSLN treatment.
Zr-MSLN PET imaging reflected MSLN expression and matched
Th-MSLN tumor uptake and biodistribution. Our data support the clinical exploration of
Zr-MSLN PET imaging together with
Th-MSLN therapy, both using the same antibody-chelator conjugate. |
Author | Ellingsen, Christine Hagemann, Urs B Suurs, Frans V Giesen, Danique Kristian, Alexander Cole, Patricia E de Vries, Elisabeth G E Lub-de Hooge, Marjolijn N Knapen, Daan G Moen, Ingrid Cuthbertson, Alan S Broer, Linda N de Groot, Derk-Jan A Indrevoll, Baard Waaijer, Stijn J H |
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Keywords | targeted 227Th therapy 89Zr PET imaging antibody conjugate mesothelin |
Language | English |
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Snippet | The mesothelin (MSLN)-targeted
Th conjugate is a novel α-therapy developed to treat MSLN-overexpressing cancers. We radiolabeled the same antibody-chelator... |
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SubjectTerms | Animals Apoptosis Cell Line, Tumor Chelating Agents Female Humans Immunoconjugates Mesothelin Mice Mice, Nude Ovarian Neoplasms Positron-Emission Tomography - methods Tissue Distribution Zirconium - therapeutic use |
Title | 89 Zr-3,2-HOPO-Mesothelin Antibody PET Imaging Reflects Tumor Uptake of Mesothelin-Targeted 227 Th-Conjugate Therapy in Mice |
URI | https://www.ncbi.nlm.nih.gov/pubmed/35422447 |
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