Synapse - Pharmacokinetics and biodistribution of a [(86)Zr]Zr-DFO-MSTP2109A anti-STEAP1 antibody in metastatic castration-resistant prostate cancer patients

Pharmacokinetics and biodistribution of a [(86)Zr]Zr-DFO-MSTP2109A anti-STEAP1 antibody in metastatic castration-resistant prostate cancer patients Journal Article

Authors:	O'Donoghue, J. A.; Danila, D. C.; Pandit-Taskar, N.; Beylergil, V.; Cheal, S. M.; Fleming, S. E.; Fox, J. J.; Ruan, S.; Zanzonico, P. B.; Ragupathi, G.; Lyashchenko, S. K.; Williams, S. P.; Scher, H. I.; Fine, B. M.; Humm, J. L.; Larson, S. M.; Morris, M. J.; Carrasquillo, J. A.
Article Title:	Pharmacokinetics and biodistribution of a [(86)Zr]Zr-DFO-MSTP2109A anti-STEAP1 antibody in metastatic castration-resistant prostate cancer patients
Abstract:	A six-transmembrane epithelial antigen of prostate-1 (STEAP1) is a newly identified target in prostate cancer. The use of radio-labeled STEAP1-targeting antibodies with positron emission tomography (PET) may allow for detection of sites of metastatic prostate cancer and may refine patient selection for antigen-directed therapies. This was a prospective study in seven patients with metastatic castration-resistant prostate cancer who had at least one archival biopsy that was STEAP1-positive by immunohistochemistry. Patients received intravenous injections of similar to 185 MBq and 10 mg of [Zr-89]Zr-DFO-MSTP2109A, a humanized IgG1 monoclonal antibody directed against STEAP1. PET/CT images, blood samples, and whole-body counts were monitored longitudinally in six patients. Here, we report on safety, biodistribution, pharmacokinetics, dose estimates to normal tissues, and initial tumor targeting for this group of patients. There was no significant acute or subacute toxicity. Favorable biodistribution and enhanced lesion uptake (in both bone and soft tissue) were observed on imaging using a mass of 10 mg of DFO-MSTP2109A. The best lesion discrimination was seen at the latest imaging time, a median of 6 days postadministration. Pharmacokinetics showed a median serum T-1/2 beta of 198 h, volume of central compartment of 3.54 L (similar to plasma volume), and clearance of 19.7 mL/h. The median biologic T-1/2 for whole-body retention was 469 h. The highest mean absorbed doses to normal organs (mGy/MBq) were 1.18, 1.11, 0.78, 0.73, and 0.71 for liver, heart wall, lung, kidney, and spleen, respectively. Excellent targeting of metastatic prostate sites in both bone and soft tissue was observed, with an optimal imaging time of 6 days postadministration. The liver and heart were the normal organs that experienced the highest absorbed doses. The pharmacokinetics were similar to other antibodies without major cross-reactivity with normal tissues. A more detailed analysis of lesion targeting in a larger patient population with correlation to immunohistology and standard imaging modalities has been reported.
Keywords:	prostate cancer; antigen; dosimetry; radioimmunotherapy; pet; antibody; therapy; positron; trial; positron-emission-tomography; low-grade; phase-i; zr-89; humanized monoclonal-antibody; steap1
Journal Title:	Molecular Pharmaceutics
Volume:	16
Issue:	7
ISSN:	1543-8384
Publisher:	American Chemical Society
Date Published:	2019-07-01
Start Page:	3083
End Page:	3090
Language:	English
ACCESSION:	WOS:000474475400023
DOI:	10.1021/acs.molpharmaceut.9b00326
PROVIDER:	wos
PUBMED:	31117485
PMCID:	PMC8176438
Notes:	Source: Wos