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Abstract

PURPOSE:

Mesothelin (MSLN) is frequently overexpressed in pancreatic and ovarian cancers, making it a potential drug target. We performed an(89)Zr-PET imaging study with MMOT0530A, a MSLN antibody, in conjunction with a phase I study with the antibody-drug conjugate DMOT4039A, containing MMOT0530A bound to MMAE. The aim was to study antibody tumor uptake, whole-body distribution, and relation between uptake, response to treatment, and MSLN expression.

EXPERIMENTAL DESIGN:

Before DMOT4039A treatment, patients received 37 MBq(89)Zr-MMOT0530A followed by PET/CT imaging 2, 4, and 7 days postinjection. Tracer uptake was expressed as standardized uptake value (SUV). MSLN expression was determined with immunohistochemistry (IHC) on archival tumor tissue.

RESULTS:

Eleven patients were included, 7 with pancreatic and 4 with ovarian cancer. IHC MSLN expression varied from absent to strong. Suitable tracer antibody dose was 10 mg MMOT0530A and optimal imaging time was 4 and 7 days postinjection. Tumor tracer uptake occurred in 37 lesions with mean SUVmaxof 13.1 (±7.5) on PET 4 days postinjection, with 11.5 (±7.5) in (N= 17) pancreatic and 14.5 (±8.7) in (N= 20) ovarian cancer lesions. Within patients, a mean 2.4-fold (±1.10) difference in uptake between tumor lesions existed. Uptake in blood, liver, kidneys, spleen, and intestine reflected normal antibody distribution. Tracer tumor uptake was correlated to IHC. Best response to DMOT4039A was partial response in one patient.

CONCLUSIONS:

With(89)Zr-MMOT0530A-PET, pancreatic and ovarian cancer lesions as well as antibody biodistribution could be visualized. This technique can potentially guide individualized antibody-based treatment. 

Author information

Lamberts LE1, Menke-van der Houven van Oordt CW2, Ter Weele EJ3, Bensch F1, Smeenk MM1, Voortman J2, Hoekstra OS4, Williams SP5, Fine BM6, Maslyar D6, de Jong JR7, Gietema JA1, Schröder CP1, Bongaerts AH8, Lub-de Hooge MN9, Verheul HM2, Sanabria Bohorquez SM6, Glaudemans AW7, de Vries EG10.

1Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

2Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.

3Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

4Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.

5Department of Early Clinical Development, Genentech, Inc. South San Francisco, California.

6Department of Biomedical Imaging, Genentech, Inc. South San Francisco, California.

7Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

8Department of Radiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

9Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

10Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. e.g.e.de.vries@umcg.nl.