Human Epidermal Growth Factor Receptor 2-Targeting [ 68 Ga]Ga-ABY-025 PET/CT Predicts Early Metabolic Response in Metastatic Breast Cancer.

Autor: Alhuseinalkhudhur A; Division of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; ali.alkhudhur@igp.uu.se.; Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden., Lindman H; Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden., Liss P; Division of Radiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden., Sundin T; Clinical Research and Development Unit, Uppsala University Hospital, Uppsala, Sweden., Frejd FY; Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden.; Affibody AB, Solna, Sweden., Hartman J; Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.; Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden; and., Iyer V; Division of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden., Feldwisch J; Affibody AB, Solna, Sweden., Lubberink M; Division of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.; Department of Medical Physics, Uppsala University Hospital, Uppsala, Sweden., Rönnlund C; Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.; Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden; and., Tolmachev V; Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden., Velikyan I; Division of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden., Sörensen J; Division of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Jazyk: angličtina
Zdroj: Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2023 Sep; Vol. 64 (9), pp. 1364-1370. Date of Electronic Publication: 2023 Jul 13.
DOI: 10.2967/jnumed.122.265364
Abstrakt: Imaging using the human epidermal growth factor receptor 2 (HER2)-binding tracer 68 Ga-labeled Z HER2:2891 -Cys-MMA-DOTA ([ 68 Ga]Ga-ABY-025) was shown to reflect HER2 status determined by immunohistochemistry and in situ hybridization in metastatic breast cancer (MBC). This single-center open-label phase II study investigated how [ 68 Ga]Ga-ABY-025 uptake corresponds to biopsy results and early treatment response in both primary breast cancer (PBC) planned for neoadjuvant chemotherapy and MBC. Methods: Forty patients with known positive HER2 status were included: 19 with PBC and 21 with MBC (median, 3 previous treatments). [ 68 Ga]Ga-ABY-025 PET/CT, [ 18 F]F-FDG PET/CT, and core-needle biopsies from targeted lesions were performed at baseline. [ 18 F]F-FDG PET/CT was repeated after 2 cycles of therapy to calculate the directional change in tumor lesion glycolysis (Δ-TLG). The largest lesions (up to 5) were evaluated in all 3 scans per patient. SUVs from [ 68 Ga]Ga-ABY-025 PET/CT were compared with the biopsied HER2 status and Δ-TLG by receiver operating characteristic analyses. Results: Trial biopsies were HER2-positive in 31 patients, HER2-negative in 6 patients, and borderline HER2-positive in 3 patients. The [ 68 Ga]Ga-ABY-025 PET/CT cutoff SUV max of 6.0 predicted a Δ-TLG lower than -25% with 86% sensitivity and 67% specificity in soft-tissue lesions (area under the curve, 0.74 [95% CI, 0.67-0.82]; P = 0.01). Compared with the HER2 status, this cutoff resulted in clinically relevant discordant findings in 12 of 40 patients. Metabolic response (Δ-TLG) was more pronounced in PBC (-71% [95% CI, -58% to -83%]; P < 0.0001) than in MBC (-27% [95% CI, -16% to -38%]; P < 0.0001), but [ 68 Ga]Ga-ABY-025 SUV max was similar in both with a mean SUV max of 9.8 (95% CI, 6.3-13.3) and 13.9 (95% CI, 10.5-17.2), respectively ( P = 0.10). In multivariate analysis, global Δ-TLG was positively associated with the number of previous treatments ( P = 0.0004) and negatively associated with [ 68 Ga]Ga-ABY-025 PET/CT SUV max ( P = 0.018) but not with HER2 status ( P = 0.09). Conclusion: [ 68 Ga]Ga-ABY-025 PET/CT predicted early metabolic response to HER2-targeted therapy in HER2-positive breast cancer. Metabolic response was attenuated in recurrent disease. [ 68 Ga]Ga-ABY-025 PET/CT appears to provide an estimate of the HER2 expression required to induce tumor metabolic remission by targeted therapies and might be useful as an adjunct diagnostic tool.
(© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)
Databáze: MEDLINE
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