Intra-image referencing for simplified assessment of HER2-expression in breast cancer metastases using the Affibody molecule ABY-025 with PET and SPECT.

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 [111In]-ABY-025 SPECT/CT (n = 7) or [68Ga]-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.

Measuring HER2-Receptor Expression In Metastatic Breast Cancer Using [68Ga]ABY-025 Affibody PET/CT.

PURPOSE: Positron Emission Tomography (PET) imaging of HER2 expression could potentially be used to select patients for HER2-targed therapy, predict response based on uptake and be used for monitoring. In this phase I/II study the HER2-binding Affibody molecule ABY-025 was labeled with (68)Ga-gallium ([(68)Ga]ABY-025) for PET to study effect of peptide mass, test-retest variability and correlation of quantified uptake in tumors to histopathology. EXPERIMENTAL DESIGN: Sixteen women with known metastatic breast cancer and on-going treatment were included and underwent FDG PET/CT to identify viable metastases. After iv injection of 212±46 MBq [(68)Ga]ABY-025 whole-body PET was performed at 1, 2 and 4 h. In the first 10 patients (6 with HER2-positive and 4 with HER2-negative primary tumors), [(68)Ga]ABY-025 PET/CT with two different doses of injected peptide was performed one week apart. In the last six patients (5 HER2-positive and 1 HER2-negative primary tumors), repeated [(68)Ga]ABY-025 PET were performed one week apart as a test-retest of uptake in individual lesions. Biopsies from 16 metastases in 12 patients were collected for verification of HER2 expression by immunohistochemistry and in-situ hybridization. RESULTS: Imaging 4h after injection with high peptide content discriminated HER2-positive metastases best (p<0.01). PET SUV correlated with biopsy HER2-scores (r=0.91, p<0.001). Uptake was five times higher in HER2-positive than in HER2-negative lesions with no overlap (p=0.005). The test-retest intra-class correlation was r=0.996. [(68)Ga]ABY-025 PET correctly identified conversion and mixed expression of HER2 and targeted treatment was changed in 3 of the 16 patients. CONCLUSION: [(68)Ga]ABY-025 PET accurately quantifies whole-body HER2-receptor status in metastatic breast cancer.

Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule 68Ga-ABY-025 in Breast Cancer Patients.

UNLABELLED: (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.

Home Oxygen Program review: Regionalization in Vancouver Coastal Health and British Columbia.

Since its inception in the 1980s, the Home Oxygen Program in British Columbia was centrally managed by the Ministry of Health. Initially a small program with few clients across the province, it soon became a large program with many clients and increasing expenditures. A pilot program started in Victoria (British Columbia) in 1996 demonstrated that managing the program locally could offer better client care, better contract management and significant cost savings. In 2002, the pilot's model and recommendations were implemented in British Columbia's five health authorities. The present review details the experiences of regionalizing the program in the Vancouver Coastal Health authority. After fine adjustments to the model were developed and new contracts and criteria changes made, better care for clients was provided than the previous centralized model at a reduced cost to the taxpayer.

Depuis sa création en 1980, le ministère de la Santé gérait le programme de fourniture d'oxygène à domicile de la Colombie-Britannique. Ce programme, qui se limitait au départ à quelques clients dans la province, a vite pris de l'envergure pour inclure de nombreux clients et s'associer à des dépenses croissantes. En 1996, un programme pilote lancé à Victoria (Colombie-Britannique) a démontré que sa gestion locale pouvait assurer de meilleurs soins aux patients, une meilleure gestion des contrats et d'importantes économies. En 2002, le modèle du projet pilote et les recommandations ont été mises en œuvre dans les cinq régies régionales de la Colombie-Britannique. La présente analyse détaille les expériences de régionalisation du programme au sein de la régie régionale Vancouver Coastal Health. Après des réglages de précision, de nouveaux contrats et des modifications aux critères, les clients ont profité de meilleurs soins que dans le cadre du modèle centralisé antérieur, à moindre coût pour le contribuable.

First-in-human molecular imaging of HER2 expression in breast cancer metastases using the 111In-ABY-025 affibody molecule.

UNLABELLED: 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) or -negative (n = 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.

Whole-body diffusion-weighted MRI compared with (18)F-NaF PET/CT for detection of bone metastases in patients with high-risk prostate carcinoma.

OBJECTIVE: The purpose of this study was to evaluate the accuracy of whole-body diffusion-weighted MRI (DWI) and (18)F-NaF PET/CT for detection of bone metastases in patients with high-risk prostate cancer. SUBJECTS AND METHODS: Both patient- and lesion-based analyses were performed on 49 consecutive patients (median age, 67 years; age range, 57-80 years) with recently diagnosed high-risk prostate cancer. All patients underwent bone scintigraphy, whole-body MRI including DWI and (18)F-NaF PET/CT before treatment. Bone scintigraphy, conventional MR images, and follow-up images were used as the standard of reference to evaluate (18)F-NaF PET/CT and DWI. RESULTS: On patient-based analysis, five patients had skeletal metastases on reference imaging that both DWI and (18)F-NaF PET/CT could verify, and (18)F-NaF PET/CT and DWI showed false-positive findings in four and one patient, respectively. With lesion-based analysis, (18)F-NaF PET/CT and DWI showed nine and five true-positive lesions, zero and four false-negative lesions, and seven and two false-positive lesions, respectively. Two patients with uncountable bone metastases were analyzed separately. In these patients, (18)F-NaF PET/CT showed more bone metastases than did DWI. CONCLUSION: We believe (18)F-NaF PET/CT is a sensitive modality for detection of bone metastases caused by prostate cancer. Whole-body DWI shows a higher specificity but lower sensitivity than (18)F-NaF PET/CT. Future studies with a larger patient cohort along with analyses of costs and clinical availability are needed before implementation of these methods can be considered.

Assessment of intravascular volume by transthoracic echocardiography during therapeutic hypothermia and rewarming in cardiac arrest survivors.

AIM: To study haemodynamic effects and changes in intravascular volume during hypothermia treatment, induced by ice-cold fluids and maintained by ice-packs followed by rewarming in patients after resuscitation from cardiac arrest. MATERIALS AND METHODS: In 24 patients following successful restoration of spontaneous circulation (ROSC), hypothermia was induced with infusion of 4 degrees C normal saline and maintained with ice-packs for 26 h after ROSC. This was followed by passive rewarming. Transthoracic echocardiography was performed at 12, 24 and 48 h after ROSC to evaluate ejection fraction and intravascular volume status. Central venous pressure (CVP), central venous oxygen saturation (ScvO(2)) and serum lactate were measured. Fluid balance was calculated. RESULTS: Twelve hours after ROSC, two separate raters independently estimated that 10 and 13 out of 23 patients had a decreased intravascular volume using transthoracic echocardiography. After 24 and 48 h this number had increased further to 14 and 13 out of 19 patients and 13 and 12 out of 21 patients. Calculated fluid balance was positive (4000 ml the day 1 and 2500 ml day 2). There was no difference in ejection fraction between the recording time points. Serum lactate and ScvO(2) were in the normal range when echocardiography exams were performed. CVP did not alter over time. CONCLUSIONS: Our results support the hypothesis that inducing hypothermia following cardiac arrest, using cold intravenous fluid infusion does not cause serious haemodynamic side effects. Serial transthoracic echocardiographic estimation of intravascular volume suggests that many patients are hypovolaemic during therapeutic hypothermia and rewarming in spite of a positive fluid balance.

The effectiveness of artificial neural networks in evaluating treatment plans for patients requiring external beam radiotherapy.

This study was designed to determine the ability of a neural network to use data summarized in artificial generated dose volume histograms (DVH) for the rectum to evaluate and compare different patient treatment plans for the treatment of localized prostate cancer. One radiotherapist evaluated 250 artificially generated DVHs representing the distribution of a dose of ration throughout the rectum during external radiotherapy for patients with prostatic adenocarcinoma (PAC). The data were also analyzed using the Lyman NTCP-model for assessing complication probabilities. A neural network consisting of 10 input nodes and one output node was trained to categorize the plans according to the radiotherapist's score. The volume in each isodose was used as input, and the risk for a severe complication was presented as output. The classifications made by the neural network matched those determined by the radiotherapist and the NTCP-model. All three techniques showed a high correlation between each other. Artificially generated dose volume histograms (DVH) for the rectum can be used for training a neural network for scoring rectal DVHs in treatment plans for localized prostate cancer.