Phase 1 Evaluation of [(64)Cu]DOTA-Patritumab to Assess Dosimetry, Apparent Receptor Occupancy, and Safety in Subjects with Advanced Solid Tumors

Overview

Journal Mol Imaging Biol

Publisher Springer

Specialties Molecular Biology
Radiology

Date 2015 Nov 15

PMID 26567113

Citations 30

Authors

A Craig Lockhart

Yongjian Liu

Farrokh Dehdashti

Richard Laforest

Joel Picus

Jennifer Frye

Lauren Trull

Stefanie Belanger

Madhuri Desai

Syed Mahmood

Jeanne Mendell

Michael J Welch

Barry A Siegel

Affiliations

Soon will be listed here.

Abstract

Purpose: The purpose of this study was to evaluate the safety, dosimetry, and apparent receptor occupancy (RO) of [(64)Cu]DOTA-patritumab, a radiolabeled monoclonal antibody directed against HER3/ERBB3 in subjects with advanced solid tumors.

Procedures: Dosimetry subjects (n = 5) received [(64)Cu]DOTA-patritumab and underwent positron emission tomography (PET)/X-ray computed tomography (CT) at 3, 24, and 48 h. Evaluable RO subjects (n = 3 out of 6) received [(64)Cu]DOTA-patritumab at day 1 and day 8 (after 9.0 mg/kg patritumab) followed by PET/CT at 24 h post-injection. Endpoints included safety, tumor uptake, and efficacy.

Results: The tumor SUVmax (± SD) was 5.6 ± 4.5, 3.3 ± 1.7, and 3.0 ± 1.1 at 3, 24, and 48 h in dosimetry subjects. The effective dose and critical organ dose (liver) averaged 0.044 ± 0.008 mSv/MBq and 0.46 ± 0.086 mGy/MBq, respectively. In RO subjects, tumor-to-blood ratio decreased from 1.00 ± 0.32 at baseline to 0.57 ± 0.17 after stable patritumab, corresponding to a RO of 42.1 ± 3.

Conclusions: [(64)Cu]DOTA-patritumab was safe. These limited results suggest that this PET-based method can be used to determine tumor-apparent RO.

Citing Articles

Measurement of specific and nonspecific tissue uptake of antibodies in tumor by SPECT imaging and nonlinear compartmental modeling.

Cho N, Ho J, Rosario G, Yu S, Ferl G, Boswell C EJNMMI Res. 2025; 15(1):15.

PMID: 39994098 PMC: 11850665. DOI: 10.1186/s13550-025-01207-9.

Advances and challenges in immunoPET methodology.

Mohr P, van Sluis J, Lub-de Hooge M, Lammertsma A, Brouwers A, Tsoumpas C Front Nucl Med. 2024; 4:1360710.

PMID: 39355220 PMC: 11440922. DOI: 10.3389/fnume.2024.1360710.

ImmunoPET Targeting Receptor Tyrosine Kinase: Clinical Applications.

Linguanti F, Abenavoli E, Calabretta R, Berti V, Lopci E Cancers (Basel). 2023; 15(24).

PMID: 38136430 PMC: 10741542. DOI: 10.3390/cancers15245886.

HER3: Toward the Prognostic Significance, Therapeutic Potential, Current Challenges, and Future Therapeutics in Different Types of Cancer.

Majumder A Cells. 2023; 12(21).

PMID: 37947595 PMC: 10648638. DOI: 10.3390/cells12212517.

Feasibility of Co-Targeting HER3 and EpCAM Using Seribantumab and DARPin-Toxin Fusion in a Pancreatic Cancer Xenograft Model.

Xu T, Schulga A, Konovalova E, Rinne S, Zhang H, Vorontsova O Int J Mol Sci. 2023; 24(3).

PMID: 36769161 PMC: 9917732. DOI: 10.3390/ijms24032838.

References

Goldenberg D . Monoclonal antibodies in cancer detection and therapy. Am J Med. 1993; 94(3):297-312. DOI: 10.1016/0002-9343(93)90062-t. View

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

LoRusso P, Janne P, Oliveira M, Rizvi N, Malburg L, Keedy V . Phase I study of U3-1287, a fully human anti-HER3 monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res. 2013; 19(11):3078-87. DOI: 10.1158/1078-0432.CCR-12-3051. View

Lewis M, Kao J, Anderson A, Shively J, Raubitschek A . An improved method for conjugating monoclonal antibodies with N-hydroxysulfosuccinimidyl DOTA. Bioconjug Chem. 2001; 12(2):320-4. DOI: 10.1021/bc0000886. View

Gullick W . The c-erbB3/HER3 receptor in human cancer. Cancer Surv. 1996; 27:339-49. View

Tamura K, Kurihara H, Yonemori K, Tsuda H, Suzuki J, Kono Y . 64Cu-DOTA-trastuzumab PET imaging in patients with HER2-positive breast cancer. J Nucl Med. 2013; 54(11):1869-75. DOI: 10.2967/jnumed.112.118612. View

Buck E, Eyzaguirre A, Haley J, Gibson N, Cagnoni P, Iwata K . Inactivation of Akt by the epidermal growth factor receptor inhibitor erlotinib is mediated by HER-3 in pancreatic and colorectal tumor cell lines and contributes to erlotinib sensitivity. Mol Cancer Ther. 2006; 5(8):2051-9. DOI: 10.1158/1535-7163.MCT-06-0007. View

Stabin M, Sparks R, Crowe E . OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med. 2005; 46(6):1023-7. View

Rizvi S, Visser O, Vosjan M, Van Lingen A, Hoekstra O, Zijlstra J . Biodistribution, radiation dosimetry and scouting of 90Y-ibritumomab tiuxetan therapy in patients with relapsed B-cell non-Hodgkin's lymphoma using 89Zr-ibritumomab tiuxetan and PET. Eur J Nucl Med Mol Imaging. 2012; 39(3):512-20. PMC: 3276758. DOI: 10.1007/s00259-011-2008-5. View

10.

Wakui H, Yamamoto N, Nakamichi S, Tamura Y, Nokihara H, Yamada Y . Phase 1 and dose-finding study of patritumab (U3-1287), a human monoclonal antibody targeting HER3, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014; 73(3):511-6. PMC: 3931937. DOI: 10.1007/s00280-014-2375-2. View

11.

Gala K, Chandarlapaty S . Molecular pathways: HER3 targeted therapy. Clin Cancer Res. 2014; 20(6):1410-6. PMC: 3977203. DOI: 10.1158/1078-0432.CCR-13-1549. View

12.

Ishibashi H, Suzuki T, Suzuki S, Moriya T, Kaneko C, Takizawa T . Sex steroid hormone receptors in human thymoma. J Clin Endocrinol Metab. 2003; 88(5):2309-17. DOI: 10.1210/jc.2002-021353. View

13.

Wiseman G, White C, Stabin M, Dunn W, Erwin W, Dahlbom M . Phase I/II 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin's lymphoma. Eur J Nucl Med. 2000; 27(7):766-77. DOI: 10.1007/s002590000276. View

14.

Lockhart A, Liu Y, Dehdashti F, Laforest R, Picus J, Frye J . Phase 1 Evaluation of [(64)Cu]DOTA-Patritumab to Assess Dosimetry, Apparent Receptor Occupancy, and Safety in Subjects with Advanced Solid Tumors. Mol Imaging Biol. 2015; 18(3):446-53. PMC: 5502796. DOI: 10.1007/s11307-015-0912-y. View

15.

Dijkers E, Munnink T, Kosterink J, Brouwers A, Jager P, de Jong J . Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin Pharmacol Ther. 2010; 87(5):586-92. DOI: 10.1038/clpt.2010.12. View

16.

Rajendran J, Gopal A, Fisher D, Durack L, Gooley T, Press O . Myeloablative 131I-tositumomab radioimmunotherapy in treating non-Hodgkin's lymphoma: comparison of dosimetry based on whole-body retention and dose to critical organ receiving the highest dose. J Nucl Med. 2008; 49(5):837-44. DOI: 10.2967/jnumed.107.043190. View

17.

McCarthy D, Shefer R, Klinkowstein R, Bass L, Margeneau W, Cutler C . Efficient production of high specific activity 64Cu using a biomedical cyclotron. Nucl Med Biol. 1997; 24(1):35-43. DOI: 10.1016/s0969-8051(96)00157-6. View