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Introduction
In breast carcinoma (BC), the Human epidermal growth factor receptor (HER2) status plays an important role in prognosis and treatment options. HER2 assessment is done via immunohistochemistry (IHC) or in situ hybridization. Tumor heterogeneity can be missed by these techniques. Moreover, the ASCO CAP scoring system is less suited to determine “HER2-low” disease1. Whole body PET imaging could be a solution; we here show clinical evaluation of a 68Ga-labeled, NOTA-coupled, single-domain antibody (sdAb) tracer targeting the HER2 receptor2.
Methods
Twenty patients (pts) with locally advanced or metastatic BC were included in this phase II trial to assess repeatability, tracer uptake in tumor lesions and immunogenicity. Repeatability was presented at EMIM 20223. In 16 pts, [18F]FDG-PET/CT (FDG) was performed as standard-of-care within 5 weeks of [68Ga]Ga-NOTA-anti-HER2-sdAb PET/CT (HER2-scan), and could be used for this subanalysis. HER2-scan was performed using intravenous injection of [68Ga]Ga-NOTA-anti-HER2-sdAb (121,28 ± 15,65 MBq) followed by PET/CT (Siemens Biograph Vision, 120 s per bed position and 40 s for the legs) at 90 minutes post injection (pi). Peak Standard Uptake Values (SUVpeak) of selected lesions were measured on both the FDG and HER2-scan.
Results/Discussion
Sixteen women with BC (3 HER2 +, 13 HER2-) and a mean age of 59,7y (range, 33-81) were included in this subanalysis. Looking at historical HER2 scoring, there was no correlation between uptake in HER2-scan and IHC score. Out of 13 HER2-negative pts, 9 had lesions with SUVpeak higher than 5, showing relevant tracer uptake in HER2-low disease. Within multiple pts, clear differences in SUVpeak between lesions were measured on HER2-scan, which was not present on FDG. This observation, together with the earlier-reported repeatability, indicates the potential of the tracer to assess heterogeneity. Two pts with [18F]FDG uptake in suspicious but finally non-cancerous lesions, did not show any HER2 uptake in these lesions (inflammation around breast prosthesis, tuberculosis (Fig. 1)), showing better specificity compared to [18F]FDG. In several pts, even in some HER2-low cases, disease extent was better appreciated on HER2-scan than on FDG, indicating good sensitivity of the tracer.
Conclusions
Comparison of tracer uptake in HER2-scan and FDG confirms [68Ga]Ga-NOTA-anti-HER2-sdAb as a potentially sensitive and specific tracer in breast carcinoma patients, also in HER2-low disease. HER2-scan holds promise for disease characterization and guidance of treatment decisions in HER2-low BC pts who could be candidates for novel HER2-targeted antibody-drug conjugate treatment.
In breast carcinoma (BC), the Human epidermal growth factor receptor (HER2) status plays an important role in prognosis and treatment options. HER2 assessment is done via immunohistochemistry (IHC) or in situ hybridization. Tumor heterogeneity can be missed by these techniques. Moreover, the ASCO CAP scoring system is less suited to determine “HER2-low” disease1. Whole body PET imaging could be a solution; we here show clinical evaluation of a 68Ga-labeled, NOTA-coupled, single-domain antibody (sdAb) tracer targeting the HER2 receptor2.
Methods
Twenty patients (pts) with locally advanced or metastatic BC were included in this phase II trial to assess repeatability, tracer uptake in tumor lesions and immunogenicity. Repeatability was presented at EMIM 20223. In 16 pts, [18F]FDG-PET/CT (FDG) was performed as standard-of-care within 5 weeks of [68Ga]Ga-NOTA-anti-HER2-sdAb PET/CT (HER2-scan), and could be used for this subanalysis. HER2-scan was performed using intravenous injection of [68Ga]Ga-NOTA-anti-HER2-sdAb (121,28 ± 15,65 MBq) followed by PET/CT (Siemens Biograph Vision, 120 s per bed position and 40 s for the legs) at 90 minutes post injection (pi). Peak Standard Uptake Values (SUVpeak) of selected lesions were measured on both the FDG and HER2-scan.
Results/Discussion
Sixteen women with BC (3 HER2 +, 13 HER2-) and a mean age of 59,7y (range, 33-81) were included in this subanalysis. Looking at historical HER2 scoring, there was no correlation between uptake in HER2-scan and IHC score. Out of 13 HER2-negative pts, 9 had lesions with SUVpeak higher than 5, showing relevant tracer uptake in HER2-low disease. Within multiple pts, clear differences in SUVpeak between lesions were measured on HER2-scan, which was not present on FDG. This observation, together with the earlier-reported repeatability, indicates the potential of the tracer to assess heterogeneity. Two pts with [18F]FDG uptake in suspicious but finally non-cancerous lesions, did not show any HER2 uptake in these lesions (inflammation around breast prosthesis, tuberculosis (Fig. 1)), showing better specificity compared to [18F]FDG. In several pts, even in some HER2-low cases, disease extent was better appreciated on HER2-scan than on FDG, indicating good sensitivity of the tracer.
Conclusions
Comparison of tracer uptake in HER2-scan and FDG confirms [68Ga]Ga-NOTA-anti-HER2-sdAb as a potentially sensitive and specific tracer in breast carcinoma patients, also in HER2-low disease. HER2-scan holds promise for disease characterization and guidance of treatment decisions in HER2-low BC pts who could be candidates for novel HER2-targeted antibody-drug conjugate treatment.
| Originele taal-2 | English |
|---|---|
| Status | Published - 2023 |
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