Diagnostic HER2-binding radiopharmaceutical, [68Ga]Ga-ABY-025, for routine clinical use in breast cancer patients

Abstract

[68Ga]Ga-ABY-025/PET-CT targeting human epidermal growth factor receptor type 2 (HER2) has demonstrated its potential clinical value for the detection and quantification of HER2 in a phase I clinical study with breast cancer patients. Previously, the radiopharmaceutical was prepared manually, however larger scale of multicenter clinical trials and routine healthcare requires automation of the production process to limit the operator radiation dose, improve tracer manufacturing robustness, and provide on-line documentation for good manufacturing practice (GMP) compliance. The production of [68Ga]Ga-ABY-025 was implemented on the Modular-Lab PharmTrace synthesis platform (Eckert & Ziegler) and disposable cassettes were developed. Pharmaceutical grade 68Ge/68Ga generator (GalliaPharm®) was used in the study. The active pharmaceutical ingredient starting material ABY-025 (GMP grade) was provided by Affibody AB. The patient examinations were conducted using a Discovery MI PET/CT scanner (20 cm FOV, GE Healthcare). Reproducible and GMP compliant fully automated production of [68Ga]Ga-ABY-025 was developed. The radiochemical purity of the product was 98.7 ± 0.6% with total peptide content of 315 ± 15 µg (n = 3). Radionuclidic purity, sterility, endotoxin content, residual solvent content, and sterile filter integrity were controlled and met acceptance criteria. The product was stable at ambient temperature for at least 2 h. The primary tumor and metastasis were detected with SUVmax values of 8.3 and 16.0, respectively. Automated production of [68Ga]Ga-ABY-025 was established and the process was validated enabling standardized multicenter phase II and III clinical trials and routine clinical use. Patient examinations conformed to the radiopharmaceutical biodistribution observed in the previous phase I study.

Keywords: Affibody; GMP; HER2; breast cancer; clinical study; gallium-68.

Conflict of interest statement

Fredrik Frejd and Joachim Feldwisch are employees of Affibody AB. Philip Schweighöfer and Johanna Seemann are employees of Eckert & Ziegler.

Figures

Figure 1

Flow chart of [68Ga]Ga-ABY-025 production on the Modular-Lab PharmTracer.

Figure 2

A. Typical HPLC-chromatograms of quality control with UV absorption profile (upper panel) and radioactivity signal profile (lower panel) of [68Ga]Ga-ABY-025; B. UV-HPLC signal calibration of ABY-025 (R2 = 0.9996).

Figure 3

Maximum intensity projection PET images of whole body scan with [68Ga]Ga-ABY-025 (A, 2 h) and [18F]FDG (D). Transaxial PET-CT fused images of the primary tumor (B, E, respectively for [68Ga]Ga-ABY-025 (2 h) and [18F]FDG) and metastasis (C, F, respectively for [68Ga]Ga-ABY-025 (2 h) and [18F]FDG). The black and white arrows indicate known tumor deposits. The red arrow (D, F) indicate post-surgical inflammation after biopsy wherein sentinel lymph node was tumor- and HER2-negative.