Phase I Study of 68Ga-HER2-Nanobody for PET/CT Assessment of HER2 Expression in Breast Carcinoma
| Autor: | Ilse Vaneycken, Catarina Xavier, Chloé Ackaert, Nick Devoogdt, Christian Vanhove, Thierry Gevaert, Christel Fontaine, Tony Lahoutte, Hendrik Everaert, Denis Schallier, François Duhoux, Johannes Heemskerk, Marian Vanhoeij, Jan Lamote, Marleen Keyaerts, Vicky Caveliers, Philippe Simon, Jacques De Greve |
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| Přispěvatelé: | Supporting clinical sciences, Medical Imaging, Nuclear Medicine, Clinical sciences, Translational Imaging Research Alliance, Department of Bio-engineering Sciences, Surgical clinical sciences, Surgery, Faculty of Economic and Social Sciences and Solvay Business School, Human Physiology and Special Physiology of Physical Education, Medical Oncology, Laboratory of Molecular and Medical Oncology, Faculty of Arts and Philosophy, Translational Radiation Oncology and Physics, Radiation Therapy, Laboratory for Medical and Molecular Oncology, Medical Genetics |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Receptor ErbB-2 RECEPTOR-SPECIFIC NANOBODY THERAPY Multimodal Imaging Metastasis 0302 clinical medicine PLUS BIODISTRIBUTION Medicine and Health Sciences Tissue Distribution breast carcinoma medicine.diagnostic_test DOSIMETRY Middle Aged CANCER Primary tumor Gene Expression Regulation Neoplastic TRASTUZUMAB EMTANSINE Positron emission tomography 030220 oncology & carcinogenesis Female Safety Breast carcinoma Adult Biodistribution PET/CT Breast Neoplasms Gallium Radioisotopes 03 medical and health sciences Breast cancer HER2 Biopsy medicine Humans Radiology Nuclear Medicine and imaging Aged METASTATIC SITES PET-CT LESIONS business.industry Biological Transport phase I Single-Domain Antibodies medicine.disease 030104 developmental biology Positron-Emission Tomography Nanobody Nuclear medicine business Tomography X-Ray Computed |
| Zdroj: | JOURNAL OF NUCLEAR MEDICINE |
| ISSN: | 1535-5667 0161-5505 |
| Popis: | UNLABELLED: Human epidermal growth factor receptor 2 (HER2) status is one of the major tumor characteristics in breast cancer to guide therapy. Anti-HER2 treatment has clear survival advantages in HER2-positive breast carcinoma patients. Heterogeneity in HER2 expression between primary tumor and metastasis has repeatedly been described, resulting in the need to reassess HER2 status during the disease course. To avoid repeated biopsy with potential bias due to tumor heterogeneity, Nanobodies directed against HER2 have been developed as probes for molecular imaging. Nanobodies, which are derived from unique heavy-chain-only antibodies, are the smallest antigen-binding antibody fragments and have ideal characteristics for PET imaging. The primary aims were assessment of safety, biodistribution, and dosimetry. The secondary aim was to investigate tumor-targeting potential. METHODS: In total, 20 women with primary or metastatic breast carcinoma (score of 2+ or 3+ on HER2 immunohistochemical assessment) were included. Anti-HER2-Nanobody was labeled with (68)Ga via a NOTA derivative. Administered activities were 53-174 MBq (average, 107 MBq). PET/CT scans for dosimetry assessment were obtained at 10, 60, and 90 min after administration. Physical evaluation and blood analysis were performed for safety evaluation. Biodistribution was analyzed for 11 organs using MIM software; dosimetry was assessed using OLINDA/EXM. Tumor-targeting potential was assessed in primary and metastatic lesions. RESULTS: No adverse reactions occurred. A fast blood clearance was observed, with only 10% of injected activity remaining in the blood at 1 h after injection. Uptake was seen mainly in the kidneys, liver, and intestines. The effective dose was 0.043 mSv/MBq, resulting in an average of 4.6 mSv per patient. The critical organ was the urinary bladder wall, with a dose of 0.406 mGy/MBq. In patients with metastatic disease, tracer accumulation well above the background level was demonstrated in most identified sites of disease. Primary lesions were more variable in tracer accumulation. CONCLUSION: (68)Ga-HER2-Nanobody PET/CT is a safe procedure with a radiation dose comparable to other routinely used PET tracers. Its biodistribution is favorable, with the highest uptake in the kidneys, liver, and intestines but very low background levels in all other organs that typically house primary breast carcinoma or tumor metastasis. Tracer accumulation in HER2-positive metastases is high, compared with normal surrounding tissues, and warrants further assessment in a phase II trial. |
| Databáze: | OpenAIRE |
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