EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds.

Primary liver tumours (i.e. hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC)) are among the most frequent cancers worldwide. However, only 10-20% of patients are amenable to curative treatment, such as resection or transplant. Liver metastases are most frequently caused by colorectal cancer, which accounts for the second most cancer-related deaths in Europe. In both primary and secondary tumours, radioembolization has been shown to be a safe and effective treatment option. The vast potential of personalized dosimetry has also been shown, resulting in markedly increased response rates and overall survival. In a rapidly evolving therapeutic landscape, the role of radioembolization will be subject to changes. Therefore, the decision for radioembolization should be taken by a multidisciplinary tumour board in accordance with the current clinical guidelines. The purpose of this procedure guideline is to assist the nuclear medicine physician in treating and managing patients undergoing radioembolization treatment. PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide among individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. These guidelines are intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set out in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognised that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

177Lu radiolabeling and preclinical theranostic study of 1C1m-Fc: an anti-TEM-1 scFv-Fc fusion protein in soft tissue sarcoma.

PURPOSE: TEM-1 (tumor endothelial marker-1) is a single-pass transmembrane cell surface glycoprotein expressed at high levels by tumor vasculature and malignant cells. We aimed to perform a preclinical investigation of a novel anti-TEM-1 scFv-Fc fusion antibody, 1C1m-Fc, which was radiolabeled with 177Lu for use in soft tissue sarcomas models. METHODS: 1C1m-Fc was first conjugated to p-SCN-Bn-DOTA using different excess molar ratios and labeled with 177Lu. To determine radiolabeled antibody immunoreactivity, Lindmo assays were performed. The in vivo behavior of [177Lu]Lu-1C1m-Fc was characterized in mice bearing TEM-1 positive (SK-N-AS) and negative (HT-1080) tumors by biodistribution and single-photon emission SPECT/CT imaging studies. Estimated organ absorbed doses were obtained based on biodistribution results. RESULTS: The DOTA conjugation and the labeling with 177Lu were successful with a radiochemical purity of up to 95%. Immunoreactivity after radiolabeling was 86% ± 4%. Biodistribution showed a specific uptake in TEM-1 positive tumor versus liver as critical non-specific healthy organ, and this specificity is correlated to the number of chelates per antibody. A 1.9-fold higher signal at 72 h was observed in SPECT/CT imaging in TEM-1 positive tumors versus control tumors. CONCLUSION: TEM-1 is a promising target that could allow a theranostic approach to soft-tissue sarcoma, and 1C1m-Fc appears to be a suitable targeting candidate. In this study, we observed the influence of the ratio DOTA/antibody on the biodistribution. The next step will be to investigate the best conjugation to achieve an optimal tumor-to-organ radioactivity ratio and to perform therapy in murine xenograft models as a prelude to future translation in patients.

Generalized SDNR analysis based on signal and noise power.

The standard approach to signal difference-to-noise ratio (SDNR) analysis requires a region of interest (ROI) positioned within the object to measure signal-difference, restricting this metric to flat-topped objects with large, sharply delineated areas. This work develops a generalized expression for SDNR (SDNRg) calculated from a ROI encompassing the object. Signal power, defined as the deviation of pixel values from the mean background due to the object, is used instead of signal-difference. Comparison was first made by simulating ideal flat-topped discs with sharp edges and diameters between 1 and 80 pixels, into a uniformly noisy background using a known signal-difference. For discs covering more than 20 pixels, SDNRg and standard SDNR (SDNRst) were within 3%, while for discs of less than 20 pixels, SDNRg was within 26% of the truth compared to 58% for SDNRst. Generalized and standard SDNR were compared for radiography images of three different phantoms with microcalcification-like objects (MTM-100 phantom), hemispheric objects of different thicknesses with a Gaussian intensity distribution and mammography quality control (QC) images. Applied to Gaussian details, SDNRg was between 20% and 45% higher than SDNRst, depending on object thickness, while for the QC images, SDNRg was with 1.7% of the standard SDNR. Compared to the standard SDNR, SDNRg is applicable to non-uniform signals, where an explicit contrast measurement is not suitable, and has improved accuracy when assessing SDNR of small objects.

Cardiac PET/CT with Rb-82: optimization of image acquisition and reconstruction parameters.

BACKGROUND: Our aim was to characterize the influence of time-of-flight (TOF) and point spread function (PSF) recovery corrections, as well as ordered subset expectation maximization (OSEM) reconstruction parameters, in 82Rb PET/CT quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR). Rest and stress list-mode dynamic 82Rb PET acquisition data from 10 patients without myocardial flow defects and 10 patients with myocardial blood flow defects were reconstructed retrospectively. OSEM reconstructions were performed with Gaussian filters of 4, 6, and 8 mm, different iterations, and subset numbers (2 × 24; 2 × 16; 3 × 16; 4 × 16). Rest and stress global, regional, and segmental MBF and MFR were computed from time activity curves with FlowQuant© software. Left ventricular segmentation using the 17-segment American Heart Association model was obtained. RESULTS: Whole left ventricle (LV) MBF at rest and stress were 0.97 ± 0.30 and 2.30 ± 1.00 mL/min/g, respectively, and MFR was 2.40 ± 1.13. Concordance was excellent and all reconstruction parameters had no significant impact on MBF, except for the exclusion of TOF which led to significantly decreased concordance in rest and stress MBF in patients with or without perfusion defects on a coronary artery basis and in MFR in patients with perfusion defects. CONCLUSIONS: Changes in reconstruction parameters in perfusion 82Rb PET/CT studies influence quantitative MBF analysis. The inclusion of TOF information in the tomographic reconstructions had significant impact in MBF quantification.

Suprathermal electron studies in the TCV tokamak: design of a tomographic hard-x-ray spectrometer.

Electron cyclotron resonance heating and electron cyclotron current drive, disruptive events, and sawtooth activity are all known to produce suprathermal electrons in fusion devices, motivating increasingly detailed studies of the generation and dynamics of this suprathermal population. Measurements have been performed in the past years in the tokamak a configuration variable (TCV) tokamak using a single pinhole hard-x-ray (HXR) camera and electron-cyclotron-emission radiometers, leading, in particular, to the identification of the crucial role of spatial transport in the physics of ECCD. The observation of a poloidal asymmetry in the emitted suprathermal bremsstrahlung radiation motivates the design of a proposed new tomographic HXR spectrometer reported in this paper. The design, which is based on a compact modified Soller collimator concept, is being aided by simulations of tomographic reconstruction. Quantitative criteria have been developed to optimize the design for the greatly variable shapes and positions of TCV plasmas.