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Kinetic analysis of HER2-binding ABY-025 Affibody molecule using dynamic PET in patients with metastatic breast
Ali Alhuseinalkhudhur1,2, Mark Lubberink3, Henrik Lindman4
1Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. ali.alkhudhur@igp.uu.se.
Background:
High expression of human epidermal growth factor receptor type 2 (HER2) represents an aggressive subtype of breast cancer. Anti-HER2 treatment requires a theragnostic approach wherein sufficiently high receptor expression in biopsy material is mandatory. Heterogeneity and discordance of HER2 expression between primary tumour and metastases, as well as within a lesion, present a complication for the treatment and require multiple biopsies. Molecular imaging using the HER2-targeting Affibody peptide ABY-025 radiolabelled with 68Ga-gallium for PET/CT is currently under investigation as a non-invasive tool for whole-body evaluation of metastatic HER2 expression. Initial studies demonstrated a high correlation between 68Ga-ABY-025 standardized uptake values (SUVs) and histopathology. However, detecting small liver lesions might be compromised by high background uptake. This study aimed to explore the applicability of kinetic modelling and parametric image analysis for absolute quantification of 68Ga-ABY-025 uptake and HER2-receptor expression and how that relates to static SUVs.
Methods:
Dynamic 68Ga-ABY-025 PET of the upper abdomen was performed 0-45 min post-injection in 16 patients with metastatic breast cancer. Five patients underwent two examinations to test reproducibility. Parametric images of tracer delivery (K1) and irreversible binding (Ki) were created with an irreversible two-tissue compartment model and Patlak graphical analysis using an image-derived input function from the descending aorta. A volume of interest (VOI)-based analysis was performed to validate parametric images. SUVs were calculated from 2 h and 4 h post-injection static whole-body images and compared to Ki.
Results:
Characterization of HER2 expression in smaller liver metastases was improved using parametric images. Ki values from parametric images agreed very well with VOI-based gold standard (R2 > 0.99, p < 0.001). SUVs of metastases at 2 h and 4 h post-injection were highly correlated with Ki values from both the two-tissue compartment model and Patlak method (R2 = 0.87 and 0.95, both p < 0.001). 68Ga-ABY-025 PET yielded high test-retest reliability (relative repeatability coefficient for Patlak 30% and for the two-tissue compartment model 47%).
Conclusion:
68Ga-ABY-025 binding in HER2-positive metastases was well characterized by irreversible two-tissue compartment model wherein Ki highly correlated with SUVs at 2 and 4 h. Dynamic scanning with parametric image formation can be used to evaluate metastatic HER2 expression accurately.
Insights
Dynamic PET imaging with 68Ga-ABY-025 accurately quantifies HER2 expression in metastatic breast cancer. Kinetic modeling improves detection of small lesions, offering a reliable theranostic approach for HER2-positive disease.
Area of Science:
- Oncology
- Nuclear Medicine
- Radiochemistry
Background:
- High human epidermal growth factor receptor type 2 (HER2) expression defines an aggressive breast cancer subtype requiring theranostic anti-HER2 treatment.
- Tumor heterogeneity and discordance in HER2 expression necessitate accurate, non-invasive methods for assessing receptor status across metastases.
- 68Ga-ABY-025 PET/CT is being investigated for whole-body HER2 evaluation, but high background uptake can hinder detection of small lesions.
Purpose of the Study:
- To evaluate the utility of kinetic modeling and parametric imaging for absolute quantification of 68Ga-ABY-025 uptake in metastatic breast cancer.
- To assess the relationship between quantitative parameters (K1, Ki) and static standardized uptake values (SUVs) derived from PET/CT imaging.
- To determine if kinetic modeling improves the characterization of HER2 expression, particularly in small liver metastases.
Main Methods:
- Dynamic 68Ga-ABY-025 PET scans of the upper abdomen were acquired from 0-45 minutes post-injection in 16 metastatic breast cancer patients.
- Parametric images of tracer delivery (K1) and irreversible binding (Ki) were generated using a two-tissue compartment model and Patlak analysis with an image-derived input function.
- Volume of interest (VOI)-based analysis validated parametric images, and static SUVs were calculated at 2 and 4 hours post-injection for comparison with Ki values.
Main Results:
- Parametric imaging enhanced the characterization of HER2 expression in small liver metastases.
- Ki values from parametric images showed excellent agreement with VOI-based analysis (R² > 0.99).
- Static SUVs at 2 and 4 hours strongly correlated with Ki values (R² = 0.87 and 0.95, respectively), demonstrating high test-retest reliability.
Conclusions:
- The irreversible two-tissue compartment model effectively characterized 68Ga-ABY-025 binding in HER2-positive metastases, with Ki correlating strongly with later static SUVs.
- Dynamic PET scanning with parametric image formation provides an accurate method for evaluating metastatic HER2 expression.
- This approach offers a promising non-invasive tool for theranostic assessment in HER2-positive metastatic breast cancer.
