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Intra-image referen...
Intra-image referencing for simplified assessment of HER2-expression in breast cancer metastases using the Affibody molecule ABY-025 with PET and SPECT.
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Sandberg, Dan T (författare)
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Tolmachev, Vladimir (författare)
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Velikyan, Irina 1966- (författare)
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Olofsson, Helena (författare)
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Wennborg, Anders (författare)
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Feldwisch, Joachim (författare)
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Carlsson, Jörgen 1944- (författare)
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Lindman, Henrik (författare)
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Sörensen, Jens (författare)
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- 2017
- 2017
- Engelska.
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - 1619-7070. ; 44:8, 1337-1346
Abstract
Ämnesord
Stäng
- PURPOSE: In phase I/II-studies radiolabelled ABY-025 Affibody molecules identified human epidermal growth factor receptor 2 (HER2) expression in breast cancer metastases using PET and SPECT imaging. Here, we wanted to investigate the utility of a simple intra-image normalization using tumour-to-reference tissue-ratio (T/R) as a HER2 status discrimination strategy to overcome potential issues related to cross-calibration of scanning devices. METHODS: Twenty-three women with pre-diagnosed HER2-positive/negative metastasized breast cancer were scanned with [(111)In]-ABY-025 SPECT/CT (n = 7) or [(68)Ga]-ABY-025 PET/CT (n = 16). Uptake was measured in all metastases and in normal spleen, lung, liver, muscle, and blood pool. Normal tissue uptake variation and T/R-ratios were established for various time points and for two different doses of injected peptide from a total of 94 whole-body image acquisitions. Immunohistochemistry (IHC) was used to verify HER2 expression in 28 biopsied metastases. T/R-ratios were compared to IHC findings to establish the best reference tissue for each modality and each imaging time-point. The impact of shed HER2 in serum was investigated. RESULTS: Spleen was the best reference tissue across modalities, followed by blood pool and lung. Spleen-T/R was highly correlated to PET SUV in metastases after 2 h (r = 0.96, P < 0.001) and reached an accuracy of 100% for discriminating IHC HER2-positive and negative metastases at 4 h (PET) and 24 h (SPECT) after injection. In a single case, shed HER2 resulted in intense tracer retention in blood. In the remaining patients shed HER2 was elevated, but without significant impact on ABY-025 biodistribution. CONCLUSION: T/R-ratios using spleen as reference tissue accurately quantify HER2 expression with radiolabelled ABY-025 imaging in breast cancer metastases with SPECT and PET. Tracer binding to shed HER2 in serum might affect quantification in the extreme case.
Ämnesord
- Medical and Health Sciences (hsv)
- Medicin och hälsovetenskap (hsv)
Nyckelord
- Affibody
- HER2-receptor
- PET
- SPECT
- Shedding
- T/R
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