99mTc­labeled single-domain antibody for SPECT/CT assessment of HER2 expression in diverse cancer types.

The expression status of human epidermal growth factor receptor 2 (HER2) in cancer predicts response to HER2-targeted therapy. Therefore, its accurate determination is of utmost importance. In recent years, there has been an increase in research on noninvasive techniques for molecular imaging, as this method offers the advantages of a more accurate determination of HER2 status without the need for multiple biopsies. The technetium-labeled single-domain antibody RAD201, previously known as 99mTc-NM-02, has been shown to be safe for use in breast cancer imaging with reasonable radiation doses, favorable biodistribution, and imaging characteristics. METHODS: A total of six HER2-positive, heavily pretreated patients with different cancer types aged between 42 and 69 years (5 women and 1 man; the median age of 55.5) have been examined. In six of seven scans, the patients were administered 500 ml of Gelofusine® solution (40 mg/ml) for radiation protection before the tracer injection (434 ± 42 MBq). Planar scans were acquired with the patient supine at 10 min, 60 min, 160 min, 20 h, and 24 h after injection. A CT scan was acquired at 95 min, followed by local tomographic SPECT imaging. RESULTS: One patient was scanned twice with RAD201, 3 months apart, resulting in a total of seven scans for six patients. Here, we show that the use of RAD201 in our patient group shows the same favorable biodistribution as in a previous study with RAD201 (NCT04040686) and that the radiation dose to the critical organ kidney can be reduced by the application of the plasma expander Gelofusine® by almost 50%. CONCLUSION: RAD201 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.

Contrast medium injection protocol adjusted for body surface area in combined PET/CT.

OBJECTIVES: To evaluate the effect of contrast medium dose adjustment for body surface area (BSA) compared with a fixed-dose protocol in combined positron emission tomography (PET) and computed tomography (CT) (PET/CT). METHODS: One hundred and twenty patients were prospectively included for (18)F-2-deoxy-fluor-glucose ((18)F-FDG)-PET/CT consisting of a non-enhanced and a venous contrast-enhanced CT, both used for PET attenuation correction. The first 60 consecutive patients received a fixed 148-ml contrast medium dose. The second 60 patients received a dose that was based on their calculated BSA. Mean and maximum standardised FDG uptake (SUVmean and SUVmax) and contrast enhancement (HU) were measured at multiple anatomical sites and PET reconstructions were evaluated visually for image quality. RESULTS: A decrease in the variance of contrast enhancement in the BSA group compared with the fixed-dose group was seen at all anatomical sites. Comparison of tracer uptake SUVmean and SUVmax between the fixed and the BSA group revealed no significant differences at all anatomical sites (all P > 0.05). Comparison of the overall image quality scores between the fixed and the BSA group showed no significant difference (P = 0.753). CONCLUSIONS: BSA adjustment results in increased interpatient homogeneity of contrast enhancement without affecting PET values. In combined PET/CT, a BSA adjusted contrast medium protocol should be used preferably. KEY POINTS: • Intravenous contrast medium is essential for many applications of PET/CT • Body surface area adjustment of contrast medium helps standardise contrast enhancement • Underdosing or overdosing of contrast medium will be reduced • PET image quality is not influenced • BSA adjusted contrast medium protocol should be used preferably in combined PET/CT.

Simultaneous dual-isotope SPECT/CT with (99m)Tc- and (111)In-labelled albumin microspheres in treatment planning for SIRT.

OBJECTIVES: To investigate simultaneous dual-isotope SPECT/CT with two differently radioisotope-labelled albumin-microsphere fractions for treatment planning of hepatic radioembolisation. METHODS: In addition to (99m)Technetium-labelled albumin microspheres (commercially available), we performed labelling with (111)Indium. Binding stability of (111)Indium-labelled microspheres was tested in vitro and in vivo in mice. Simultaneous dual-isotope SPECT/CT imaging was validated in an anthropomorphic torso phantom; subsequently, dual-isotope SPECT/CT was performed under in-vivo conditions in pigs (n = 3) that underwent transarterial injection of (99m)Technetium- and (111)Indium-labelled microspheres in the liver (right and left hepatic artery, respectively), in both kidneys and in the gluteal musculature. In total, n = 18 transarterial injections were performed. RESULTS: In-vitro testing and in-vivo studies in mice documented high binding stability for both (99m)Technetium-labelled and (111)Indium-labelled microsphere fractions. In phantom studies, simultaneous dual-isotope SPECT/CT enabled reliable separation of both isotopes. In pigs, the identified deposition of both isotopes could be accurately matched with intended injection targets (100 %, 18/18 intended injection sites). Furthermore, an incidental deposition of (99m)Technetium-labelled microspheres in the stomach could be correlated to the test injection into a right hepatic artery. CONCLUSION: Simultaneous dual-isotope SPECT/CT after transarterial injection with (99m)Technetium- and (111)Indium-labelled microspheres is feasible. Thus, it may offer additional, valuable information compared to single (99m)Technetium-labelled albumin examinations. KEY POINTS: • Simultaneous dual-isotope SPECT/CT with (111) In- and (99m) Tc-labelled albumin microspheres is feasible. • Differentiation of two microsphere fractions after transarterial injection is possible. • The origin of an extra-hepatic microsphere deposition can be correlated to the corresponding artery. • This technique could reduce the setup time for selective internal radiation treatment.

Activity quantification combining conjugate-view planar scintigraphies and SPECT/CT data for patient-specific 3-D dosimetry in radionuclide therapy.

PURPOSE: Three-dimensional dosimetry based on quantitative SPECT/CT has potential advantages over planar approaches, but may be impractical due to acquisition durations. We combine one SPECT/CT with improved quantification of multiple planar scintigraphies to shorten acquisitions. METHODS: A hybrid 2-D/3-D quantification technique is proposed, using SPECT/CT information for robust planar image quantification and creating virtual SPECTs out of conjugate-view planar scintigraphies; these are included in a 3-D absorbed dose calculation. A projection model simulates photon attenuation and scatter as well as camera and collimator effects. Planar and SPECT calibration techniques are described, offering multiple pathways of deriving calibration factors for hybrid quantification. Model, phantom and patient data are used to validate the approach on a per-organ basis, and the similarity of real and virtual SPECTs, and of planar images and virtual SPECT projections, is assessed using linear regression analysis. RESULTS: Organ overlap, background activity and organ geometry are accounted for in the algorithm. Hybrid time-activity curves yield the same information as those derived from a conventional SPECT evaluation. Where correct values are known, hybrid quantification errors are less than 16% for all but two compartments (SPECT/CT 23%). Under partial volume effects, hybrid quantification can provide more robust results than SPECT/CT. The mean correlation coefficient of 3-D data is 0.962 (2-D 0.934). As a consequence of good activity quantification performance, good agreement of absorbed dose estimates and dose-volume histograms with reference results is achieved. CONCLUSION: The proposed activity quantification method for 2-D scintigraphies can speed up SPECT/CT-based 3-D dosimetry without losing accuracy.

Robust real-time extraction of respiratory signals from PET list-mode data.

Respiratory motion, which typically cannot simply be suspended during PET image acquisition, affects lesions' detection and quantitative accuracy inside or in close vicinity to the lungs. Some motion compensation techniques address this issue via pre-sorting ('binning') of the acquired PET data into a set of temporal gates, where each gate is assumed to be minimally affected by respiratory motion. Tracking respiratory motion is typically realized using dedicated hardware (e.g. using respiratory belts and digital cameras). Extracting respiratory signals directly from the acquired PET data simplifies the clinical workflow as it avoids handling additional signal measurement equipment. We introduce a new data-driven method 'combined local motion detection' (CLMD). It uses the time-of-flight (TOF) information provided by state-of-the-art PET scanners in order to enable real-time respiratory signal extraction without additional hardware resources. CLMD applies center-of-mass detection in overlapping regions based on simple back-positioned TOF event sets acquired in short time frames. Following a signal filtering and quality-based pre-selection step, the remaining extracted individual position information over time is then combined to generate a global respiratory signal. The method is evaluated using seven measured FDG studies from single and multiple scan positions of the thorax region, and it is compared to other software-based methods regarding quantitative accuracy and statistical noise stability. Correlation coefficients around 90% between the reference and the extracted signal have been found for those PET scans where motion affected features such as tumors or hot regions were present in the PET field-of-view. For PET scans with a quarter of typically applied radiotracer doses, the CLMD method still provides similar high correlation coefficients which indicates its robustness to noise. Each CLMD processing needed less than 0.4 s in total on a standard multi-core CPU and thus provides a robust and accurate approach enabling real-time processing capabilities using standard PC hardware.

Simulation-based partial volume correction for dopaminergic PET imaging: Impact of segmentation accuracy.

AIM: Partial volume correction (PVC) is an essential step for quantitative positron emission tomography (PET). In the present study, PVELab, a freely available software, is evaluated for PVC in (18)F-FDOPA brain-PET, with a special focus on the accuracy degradation introduced by various MR-based segmentation approaches. METHODS: Four PVC algorithms (M-PVC; MG-PVC; mMG-PVC; and R-PVC) were analyzed on simulated (18)F-FDOPA brain-PET images. MR image segmentation was carried out using FSL (FMRIB Software Library) and SPM (Statistical Parametric Mapping) packages, including additional adaptation for subcortical regions (SPML). Different PVC and segmentation combinations were compared with respect to deviations in regional activity values and time-activity curves (TACs) of the occipital cortex (OCC), caudate nucleus (CN), and putamen (PUT). Additionally, the PVC impact on the determination of the influx constant (Ki) was assessed. RESULTS: Main differences between tissue-maps returned by three segmentation algorithms were found in the subcortical region, especially at PUT. Average misclassification errors in combination with volume reduction was found to be lowest for SPML (PUT < 30%) and highest for FSL (PUT > 70%). Accurate recovery of activity data at OCC is achieved by M-PVC (apparent recovery coefficient varies between 0.99 and 1.10). The other three evaluated PVC algorithms have demonstrated to be more suitable for subcortical regions with MG-PVC and mMG-PVC being less prone to the largest tissue misclassification error simulated in this study. Except for M-PVC, quantification accuracy of Ki for CN and PUT was clearly improved by PVC. CONCLUSIONS: The regional activity value of PUT was appreciably overcorrected by most of the PVC approaches employing FSL or SPM segmentation, revealing the importance of accurate MR image segmentation for the presented PVC framework. The selection of a PVC approach should be adapted to the anatomical structure of interest. Caution is recommended in subsequent interpretation of Ki values. The possible different change of activity concentrations due to PVC in both target and reference regions tends to alter the corresponding TACs, introducing bias to Ki determination. The accuracy of quantitative analysis was improved by PVC but at the expense of precision reduction, indicating the potential impropriety of applying the presented framework for group comparison studies.

Study-parameter impact in quantitative 90-Yttrium PET imaging for radioembolization treatment monitoring and dosimetry.

A small positron-generating branch in 90-Yttrium ((90)Y) decay enables post-therapy dose assessment in liver cancer radioembolization treatment. The aim of this study was to validate clinical (90)Y positron emission tomography (PET) quantification, focusing on scanner linearity as well as acquisition and reconstruction parameter impact on scanner calibration. Data from three dedicated phantom studies (activity range: 55.2 MBq-2.1 GBq) carried out on a Philips Gemini TF 16 PET/CT scanner were analyzed after reconstruction with up to 361 parameter configurations. For activities above 200 MBq, scanner linearity could be confirmed with relative error margins 4%. An acquisition-time-normalized calibration factor of 1.04 MBq·s/CNTS was determined for the employed scanner. Stable activity convergence was found in hot phantom regions with relative differences in summed image intensities between -3.6% and +2.4%. Absolute differences in background noise artifacts between - 79.9% and + 350% were observed. Quantitative accuracy was dominated by subset size selection in the reconstruction. Using adequate segmentation and optimized acquisition parameters, the average activity recovery error induced by the axial scanner sensitivity profile was reduced to +2.4%±3.4% (mean ± standard deviation). We conclude that post-therapy dose assessment in (90)Y PET can be improved using adapted parameter setups.

Simultaneous reconstruction of activity and attenuation for PET/MR.

Medical investigations targeting a quantitative analysis of the position emission tomography (PET) images require the incorporation of additional knowledge about the photon attenuation distribution in the patient. Today, energy range adapted attenuation maps derived from computer tomography (CT) scans are used to effectively compensate for image quality degrading effects, such as attenuation and scatter. Replacing CT by magnetic resonance (MR) is considered as the next evolutionary step in the field of hybrid imaging systems. However, unlike CT, MR does not measure the photon attenuation and thus does not provide an easy access to this valuable information. Hence, many research groups currently investigate different technologies for MR-based attenuation correction (MR-AC). Typically, these approaches are based on techniques such as special acquisition sequences (alone or in combination with subsequent image processing), anatomical atlas registration, or pattern recognition techniques using a data base of MR and corresponding CT images. We propose a generic iterative reconstruction approach to simultaneously estimate the local tracer concentration and the attenuation distribution using the segmented MR image as anatomical reference. Instead of applying predefined attenuation values to specific anatomical regions or tissue types, the gamma attenuation at 511 keV is determined from the PET emission data. In particular, our approach uses a maximum-likelihood estimation for the activity and a gradient-ascent based algorithm for the attenuation distribution. The adverse effects of scattered and accidental gamma coincidences on the quantitative accuracy of PET, as well as artifacts caused by the inherent crosstalk between activity and attenuation estimation are efficiently reduced using enhanced decay event localization provided by time-of-flight PET, accurate correction for accidental coincidences, and a reduced number of unknown attenuation coefficients. First results achieved with measured whole body PET data and reference segmentation from CT showed an absolute mean difference of 0.005 cm⁻¹ (< 20%) in the lungs, 0.0009 cm⁻¹ (< 2%) in case of fat, and 0.0015 cm⁻¹ (< 2%) for muscles and blood. The proposed method indicates a robust and reliable alternative to other MR-AC approaches targeting patient specific quantitative analysis in time-of-flight PET/MR.