The expression status of human epidermal growth factor receptor type 2 (HER2) predicts the response of HER2-targeted therapy in breast cancer. ABY-025 is a small reengineered Affibody molecule targeting a unique epitope of the HER2 receptor, not occupied by current therapeutic agents. This study evaluated the distribution, safety, dosimetry, and efficacy of 111 In-ABY-025 for determining the HER2 status in metastatic breast cancer. Methods: Seven patients with metastatic breast cancer and HER2-positive (n 5 5) or -negative (n 5 2) primary tumors received an intravenous injection of approximately 100 μg (∼140 MBq) of 111 In-ABY-025. Planar γ-camera imaging was performed after 30 min, followed by SPECT/CT after 4, 24, and 48 h. Blood levels of radioactivity, antibodies, shed serum HER2, and toxicity markers were evaluated. Lesional HER2 status was verified by biopsies. The metastases were located by 18 F-FDG PET/CT 5 d before 111 In-ABY-025 imaging. Results: Injection of 111 In-ABY-025 yielded a mean effective dose of 0.15 mSv/MBq and was safe, well tolerated, and without drug-related adverse events. Fast blood clearance allowed high-contrast HER2 images within 4-24 h. No anti-ABY-025 antibodies were observed. When metastatic uptake at 24 h was normalized to uptake at 4 h, the ratio increased in HER2-positive metastases and decreased in negative ones (P , 0.05), with no overlap and confirmation by biopsies. In 1 patient, with HER2-positive primary tumor, 111 In-ABY-025 imaging correctly suggested a HER2-negative status of the metastases. The highest normal-tissue uptake was in the kidneys, followed by the liver and spleen. Conclusion: 111 In-ABY-025 appears safe for use in humans and is a promising noninvasive tool for discriminating HER2 status in metastatic breast cancer, regardless of ongoing HER2-targeted antibody treatment. Today,t reatment of breast cancer is based on the biologic profile of the individual tumor. Knowledge of the human epidermal growth factor receptor type 2 (HER2) status is crucial to predict the response of HER2-targeted therapy (1). Patients with breast cancer overexpressing HER2 have improved survival when treated with HER2-targeting agents such as trastuzumab, pertuzumab, and trastuzumab emtansine (2-10).The analysis of HER2 expression is usually based on a surgical specimen of the primary tumor or, in case of neoadjuvant therapy or inoperable disease, on a biopsy sample from the tumor (11). The pathologic analysis includes immunohistochemistry and in some cases fluorescence in situ hybridization (FISH). Therapy for patients with disseminated disease is often based on histopathologic classification of the primary tumor and not of the metastases. Disparities in HER2 expression of primary breast cancer and metastases have been reported. Metaanalysis of 26 studies including 2,520 patients revealed discordance in HER2 expression between the primary tumor and local lymph node metastases in the range of 2.4%-7.2% and discordance with distant metastases in the range of 6.9%-18.6%, with an abs...
The resolution and quantitative accuracy of PET are highly influenced by the reconstruction method. Penalized-likelihood estimation algorithms allow for fully convergent iterative reconstruction, generating a higher image contrast than ordered-subsets expectation maximization (OSEM) while limiting noise. In this study, a type of penalized reconstruction known as block-sequential regularized expectation maximization (BSREM) was compared with time-of-flight OSEM (TOF OSEM). Various strengths of noise penalization factor β were tested along with various acquisition durations and transaxial fields of view (FOVs) with the aim of evaluating the performance and clinical use of BSREM for F-FDG PET/CT, both quantitatively and in a qualitative visual evaluation. Eleven clinical whole-body F-FDG PET/CT examinations acquired on a digital TOF PET/CT scanner were included. The data were reconstructed using BSREM with point-spread function recovery and β-factors of 133, 267, 400, and 533-and using TOF OSEM with point-spread function-for various acquisition times per bed position and various FOVs. Noise level, signal-to-noise ratio (SNR), signal-to-background ratio (SBR), and SUV were analyzed. A masked evaluation of visual image quality, rating several aspects, was performed by 2 nuclear medicine physicians to complement the analysis. The lowest levels of noise were reached with the highest β-factor, resulting in the highest SNR, which in turn resulted in the lowest SBR. A β-factor of 400 gave noise equivalent to TOF OSEM but produced a significant increase in SUV (11%), SNR (22%), and SBR (12%). BSREM with a β-factor of 533 at a decreased acquisition duration (2 min/bed position) was comparable to TOF OSEM at a full acquisition duration (3 min/bed position). Reconstructed FOV had an impact on BSREM outcome measures; SNR increased and SBR decreased when FOV was shifted from 70 to 50 cm. The evaluation of visual image quality resulted in similar scores for reconstructions, although a β-factor of 400 obtained the highest mean whereas a β-factor of 267 was ranked best in overall image quality, contrast, sharpness, and tumor detectability. In comparison with TOF OSEM, penalized BSREM reconstruction resulted in an increased tumor SUV and an improved SNR and SBR at a matched level of noise. BSREM allowed for a shorter acquisition than TOF OSEM, with equal image quality.
68 Ga-DOTATOC and 68 Ga-DOTATATE are 2 radiolabeled somatostatin analogs for in vivo diagnosis of neuroendocrine tumors with PET. The aim of the present work was to measure their comparative biodistribution and radiation dosimetry. Methods: Ten patients diagnosed with neuroendocrine tumors were included. Each patient underwent a 45-min dynamic and 3 whole-body PET/CT scans at 1, 2, and 3 h after injection of each tracer on consecutive days. Absorbed doses were calculated using OLINDA/EXM 1.1. Results: Data from 9 patients could be included in the analysis. Of the major organs, the highest uptake at 1, 2, and 3 h after injection was observed in the spleen, followed by kidneys and liver. For both tracers, the highest absorbed organ doses were seen in the spleen and urinary bladder wall, followed by kidney, adrenals, and liver. The absorbed doses to the liver and gallbladder wall were slightly but significantly higher for 68 Ga-DOTATATE. The total effective dose was 0.021 6 0.003 mSv/MBq for both tracers. Conclusion: The effective dose for a typical 100-MBq administration of 68 Ga-DOTATATE and 68 Ga-DOTATOC is 2.1 mSv for both tracers. Therefore, from a radiation dosimetry point of view, there is no preference for either tracer for PET/CT evaluation of somatostatin receptor-expressing tumors.
68 Ga-ABY-025 is a radiolabeled Affibody molecule for in vivo diagnosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer tumors with PET. The aim of the present work was to measure the biodistribution and estimate the radiation dosimetry of 68 Ga-ABY-025 for 2 different peptide mass doses in a single group of patients using dynamic and serial whole-body PET/CT. Methods: Eight patients with metastatic breast cancer were included. Each patient underwent an abdominal 45-min dynamic and 3 whole-body PET/CT scans at 1, 2, and 4 h after injection of a low peptide dose (LD) and a high peptide dose (HD), with approximately the same amount of radioactivity, in separate investigations 1 wk apart. As input to the absorbed dose calculations, volumes of interest were drawn on all clearly identifiable source organs: liver, kidneys, spleen, descending aorta, and upper large intestine. Absorbed doses were calculated using OLINDA/EXM, version 1.1. Results: Of the major organs, the highest radionuclide uptake at 1, 2, and 4 h after injection was observed in the kidneys and liver. The highest absorbed organ doses were seen in the kidneys, followed by the liver for both LD and HD 68 Ga-ABY-025. Absorbed doses to liver and kidneys were slightly but significantly higher for LD. Total effective dose was 0.030 ± 0.003 mSv/MBq for LD and 0.028 ± 0.002 mSv/MBq for HD. Conclusion: The effective dose for a typical 200-MBq administration of 68 Ga-ABY-025 is 6.0 mSv for LD and 5.6 mSv for HD. Therefore, from a radiation dosimetry point of view, HD is preferred for PET/CT evaluation of HER2-expressing breast cancer tumors. These effective doses are somewhat higher than earlier published values for other 68 Ga-labeled tracers, such as 0.021 ± 0.003 mSv/MBq for 68 Ga-DOTATATE and 68 Ga-DOTATOC, mainly because of higher uptake in liver and kidney. Forwomen,br east cancer is currently the most common cancer.Human epidermal growth factor receptor 2 (HER2) is overexpressed in about 1 of 6 cases (1-3) at initial diagnosis and is associated with poor survival (1,3). Treatments targeted to HER2, such as with the anti-HER2 antibody trastuzumab, have considerably improved overall survival (1,3,4). Today, assessment of HER2 status is based on tumor biopsy. However, HER2 expression can vary between the primary tumor and metastases in up to 40% of cases (2,5,6) and metastatic HER2 expression can change over time, which could necessitate a change of therapy (7,8). Follow-up using biopsies cannot always be performed due to practical reasons or patient discomfort.Molecular imaging using SPECT and PET might be a noninvasive, whole-body-based way to evaluate HER2 expression quantitatively. One such approach is the use of trastuzumab labeled with 111 In (half-time, 2.8 d) (9) or 89 Zr (3.3 d) (10) for use with SPECT and PET, respectively, but the slow kinetics of antibodies require imaging several days after administration. One promising method of fast, safe, and accurate imaging that specifically binds to a site on the receptor not occu...
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