Navigating the nuances: comparative analysis and hyperparameter optimisation of neural architectures on contrast-enhanced MRI for liver and liver tumour segmentation.

In medical imaging, accurate segmentation is crucial to improving diagnosis, treatment, or both. However, navigating the multitude of available architectures for automatic segmentation can be overwhelming, making it challenging to determine the appropriate type of architecture and tune the most crucial parameters during dataset optimisation. To address this problem, we examined and refined seven distinct architectures for segmenting the liver, as well as liver tumours, with a restricted training collection of 60 3D contrast-enhanced magnetic resonance images (CE-MRI) from the ATLAS dataset. Included in these architectures are convolutional neural networks (CNNs), transformers, and hybrid CNN/transformer architectures. Bayesian search techniques were used for hyperparameter tuning to hasten convergence to the optimal parameter mixes while also minimising the number of trained models. It was unexpected that hybrid models, which typically exhibit superior performance on larger datasets, would exhibit comparable performance to CNNs. The optimisation of parameters contributed to better segmentations, resulting in an average increase of 1.7% and 5.0% in liver and tumour segmentation Dice coefficients, respectively. In conclusion, the findings of this study indicate that hybrid CNN/transformer architectures may serve as a practical substitute for CNNs even in small datasets. This underscores the significance of hyperparameter optimisation.

Validation of a discovery MI 4-ring model according to the NEMA NU 2-2018 standards: from Monte Carlo simulations to clinical-like reconstructions.

BACKGROUND: We propose a comprehensive evaluation of a Discovery MI 4-ring (DMI) model, using a Monte Carlo simulator (GATE) and a clinical reconstruction software package (PET toolbox). The following performance characteristics were compared with actual measurements according to NEMA NU 2-2018 guidelines: system sensitivity, count losses and scatter fraction (SF), coincidence time resolution (CTR), spatial resolution (SR), and image quality (IQ). For SR and IQ tests, reconstruction of time-of-flight (TOF) simulated data was performed using the manufacturer's reconstruction software. RESULTS: Simulated prompt, random, true, scatter and noise equivalent count rates closely matched the experimental rates with maximum relative differences of 1.6%, 5.3%, 7.8%, 6.6%, and 16.5%, respectively, in a clinical range of less than 10 kBq/mL. A 3.6% maximum relative difference was found between experimental and simulated sensitivities. The simulated spatial resolution was better than the experimental one. Simulated image quality metrics were relatively close to the experimental results. CONCLUSIONS: The current model is able to reproduce the behaviour of the DMI count rates in the clinical range and generate clinical-like images with a reasonable match in terms of contrast and noise.

Pre-treatment dosimetry in90Y-SIRT: Is it possible to optimise SPECT reconstruction parameters and calculation methods for accurate dosimetry?

PURPOSE: The aim of this study was (a) to optimise the99mTc-SPECT reconstruction parameters for the pre-treatment dosimetry of90Y-selective internal radiation therapy (SIRT) and (b) to compare the accuracy of clinical dosimetry methods with full Monte-Carlo dosimetry (fMCD) performed with Gate. METHODS: To optimise the reconstruction parameters, two hundred reconstructions with different parameters were performed on a NEMA phantom, varying the number of iterations, subsets, and post-filtering. The accuracy of the dosimetric methods was then investigated using an anthropomorphic phantom. Absorbed dose maps were generated using (1) the Partition Model (PM), (2) the Dose Voxel Kernel (DVK) convolution, and (3) the Local Deposition Method (LDM) with known activity restricted to the whole phantom (WP) or to the liver and lungs (LL). The dose to the lungs was calculated using the "multiple DVK" and "multiple LDM" methods. RESULTS: Optimal OSEM reconstruction parameters were found to depend on object size and dosimetric criterion chosen (Dmean or DVH-derived metric). The Dmean of all three dosimetric methods was close (≤ 10%) to the Dmean of fMCD simulations when considering large segmented volumes (whole liver, normal liver). In contrast, the Dmean to the small volume (∅=31) was systemically underestimated (12%-25%). For lungs, the "multiple DVK" and "multiple LDM" methods yielded a Dmean within 20% for the WP method and within 10% for the LL method. CONCLUSIONS: All three methods showed a substantial degradation of the dose-volume histograms (DVHs) compared to fMCD simulations. The DVK and LDM methods performed almost equally well, with the "multiple DVK" method being more accurate in the lungs.

Dealing with dry waste disposal issues associated with 177mLu impurities: a long-term challenge for nuclear medicine departments.

PURPOSE: A strategy for management of radioactive waste associated with 177Lu-dotatate (Lutathera®) treatments was established in our institution, based on predicted storage times of 3-5 years extrapolated from the results of a 2-year measurement study. The aim of this work was to validate this strategy by identifying contaminants and confirming disposal based on the clearance level twice-the-background was within expected time frames. METHODS: We conducted a prospective series of measurements of radioactive waste associated with the first 65 treatments administered. Sequential measurements of the first 45 vials used were performed on a dose calibrator to identify contaminants. Exposure rates in contact were monitored with a dose ratemeter on a 6-monthly basis for all waste stored: 46 empty vials, 19 vials partially used and 61 biohazard containers. RESULTS: Initial median activity of the first vials used was 118 MBq [4-4188 MBq]. For each vial, the decay curve of activity obtained was adjusted to a bi-exponential model. The major component, representing 99.7% of the activity, has a median half-life of 6.6 days [5.7-7.2 days] corresponding to 177Lu. The second, representing only 0.3% of the activity and having a median half-life of 152 days [104-205 days] corresponding to 177mLu, determines necessary storage times. Partially used vials can be disposed of after 5 years, other waste after 3 years. Compliance with the regulatory clearance level is achieved within expected time frames. CONCLUSION: Although only present as traces, 177mLu associated with the direct production route results in major radioactive waste disposal issues for hospitals. Availability of radiopharmaceuticals without impurities appears to be crucial for an expanding use of targeted radionuclide therapy.

A Practical Quality Assurance Procedure for Data Acquisitions in Preclinical Simultaneous PET/MR Systems.

The availability of preclinical simultaneous PET/MR imaging systems has been increasing in recent years. Therefore, this technique is progressively moving from the hands of pure physicists towards those of scientists more involved in pharmacology and biology. Unfortunately, these combined scanners can be prone to artefacts and deviation of their characteristics under the influence of external factors or mutual interference between subsystems. This may compromise the image quality as well as the quantitative aspects of PET and MR data. Hence, quality assurance is crucial to avoid loss of animals and experiments. A possible risk to the acceptance of quality control by preclinical teams is that the complexity and duration of this quality control are increased by the addition of MR and PET tests. To avoid this issue, we have selected over the past 5 years, simple tests that can be easily and quickly performed each day before starting an animal PET/MR acquisition. These tests can be performed by the person in charge of the experiment even if this person has a limited expertise in instrumentation and performance evaluation. In addition to these daily tests, other tests are suggested for an advanced system follow-up at a lower frequency. In the present paper, the proposed tests are sorted by periodicity from daily to annual. Besides, we have selected test materials that are available at moderate cost either commercially or through 3D printing.

Critical analysis of the effect of various methodologies to compute breast cancer tumour blood flow-based texture features using first-pass 18F-FDG PET.

PURPOSE: Assessment of tumour blood flow (BF) heterogeneity using first-pass FDG PET/CT and textural feature (TF) analysis is an innovative concept. We aim to explore the relationship between BF heterogeneity measured with different TFs calculation methods and the response to neoadjuvant chemotherapy (NAC) in patients with newly diagnosed breast cancer (BC). METHODS: One hundred and twenty-five patients were enrolled. Dynamic first-pass and delayed FDG PET/CT scans were performed before NAC. Nine TFs were calculated from perfusion and metabolic PET images using relative (RR) or absolute (AR) rescaling strategies with two textural matrix calculation methods. Patients were classified according to presence or absence of a pathologic complete response (pCR) after NAC. The relationship between BF texture features and conventional features were analysed using spearman correlations. The TFs' differences between pCR and non-pCR groups were evaluated using Mann-Whitney tests and descriptive factorial discriminant analysis (FDA). RESULTS: Relation between tumour BF-based TFs and global BF parameters were globally similar to those observed for tumour metabolism. None of the TFs was significantly different between pCR and non-pCR groups in the Mann-Whitney analysis, after Benjamini-Hochberg correction. Using a RR led to better discriminations between responders and non-responders in the FDA analysis. The best results were obtained by combining all the PET features, including BF ones. CONCLUSION: A better differentiation of patients reaching a pCR was observed using a RR. Moreover, BF heterogeneity might bring a useful information when combined with metabolic PET parameters to predict the pCR after neoadjuvant chemotherapy.

[123I]MIBG is a better early marker of anthracycline cardiotoxicity than [18F]FDG: a preclinical SPECT/CT and simultaneous PET/MR study.

BACKGROUND: During anthracycline treatment of cancer, there is a lack for biomarkers of cardiotoxicity besides the cardiac dysfunction. The objective of the present study was to compare [18F]FDG and [123I]MIBG (metaiodobenzylguanidine) in a longitudinal study in a doxorubicin-induced cardiotoxicity rat model. METHODS: Male Wistar Han rats were intravenously administered 3 times at 10 days' interval with saline or doxorubicin (5 mg/kg). [123I]MIBG SPECT/CT (single photon emission computed tomography-computed tomography) and simultaneous [18F]FDG PET (positron emission tomography)/7 Tesla cardiac MR (magnetic resonance) imaging acquisitions were performed at 24 h interval before first doxorubicin / saline injection and every 2 weeks during 6 weeks. At 6 weeks, the heart tissue was collected for histomorphometry measurements. RESULTS: At week 4, left ventricle (LV) end-diastolic volume was significantly reduced in the doxorubicin group. At week 6, the decreased LV end-diastolic volume was maintained, and LV end-systolic volume was increased resulting in a significant reduction of LV ejection fraction (47 ± 6% vs. 70 ± 3%). At weeks 4 and 6, but not at week 2, myocardial [18F]FDG uptake was decreased compared with the control group (respectively, 4.2 ± 0.5%ID/g and 9.2 ± 0.8%ID/g at week 6). Moreover, [18F]FDG cardiac uptake correlated with cardiac function impairment. In contrast, from week 2, a significant decrease of myocardial [123I]MIBG heart to mediastinum ratio was detected in the doxorubicin group and was maintained at weeks 4 and 6 with a 45.6% decrease at week 6. CONCLUSION: This longitudinal study precises that after doxorubicin treatment, cardiac [123I]MIBG uptake is significantly reduced as early as 2 weeks followed by the decrease of the LV end-diastolic volume and [18F]FDG uptake at 4 weeks and finally by the increase of LV end-systolic volume and decrease of LV ejection fraction at 6 weeks. Cardiac innervation imaging should thus be considered as an early key feature of anthracycline cardiac toxicity.

Impact of contouring methods on pre-treatment and post-treatment dosimetry for the prediction of tumor control and survival in HCC patients treated with selective internal radiation therapy.

INTRODUCTION: The aim of this study was to evaluate the impact of the contouring methods on dose metrics and their predictive value on tumor control and survival, in both situations of pre-treatment and post-treatment dosimetry, for patients with advanced HCC treated with SIRT. METHODS: Forty-eight patients who underwent SIRT between 2012 and 2020 were retrospectively included in this study. Target volumes were delineated using two methods: MRI-based contours manually drawn by a radiologist and then registered on SPECT/CT and PET/CT via deformable registration (Pre-CMRI and Post-CMRI), 99mTc-MAA-SPECT and 90Y-microspheres-PET 10% threshold contouring (Pre-CSPECT and Post-CPET). The mean absorbed dose (Dm) and the minimal absorbed dose delivered to 70% of the tumor volume (D70) were evaluated with both contouring methods; the tumor-to-normal liver uptake ratio (TNR) was evaluated with MRI-based contours only. Tumor response was assessed using the mRECIST criteria on the follow-up MRIs. RESULTS: No significant differences were found for Dm and TNR between pre- and post-treatment. TNR evaluated with radiologic contours (Pre-CMRI and Post-CMRI) were predictive of tumor control at 6 months on pre- and post-treatment dosimetry (OR 5.9 and 7.1, respectively; p = 0.02 and 0.01). All dose metrics determined with both methods were predictive of overall survival (OS) on pre-treatment dosimetry, but only Dm with MRI-based contours was predictive of OS on post-treatment images with a median of 23 months for patients with a supramedian Dm versus 14 months for the others (p = 0.04). CONCLUSION: In advanced HCC treated with SIRT, Dm and TNR determined with radiologic contours were predictive of tumor control and OS. This study shows that a rigorous clinical workflow (radiologic contours + registration on scintigraphic images) is feasible and should be prospectively considered for improving therapeutic strategy.

Transarterial Radioembolization of Hepatocellular Carcinoma, Liver-Dominant Hepatic Colorectal Cancer Metastases, and Cholangiocarcinoma Using Yttrium90 Microspheres: Eight-Year Single-Center Real-Life Experience.

Liver tumors are common and may be unamenable to surgery or ablative treatments. Consequently, other treatments have been devised. To assess the safety and efficacy of transarterial radioembolization (TARE) with Yttrium-90 for hepatocellular carcinoma (HCC), liver-dominant hepatic colorectal cancer metastases (mCRC), and cholangiocarcinoma (CCA), performed according to current recommendations, we conducted a single-center retrospective study in 70 patients treated with TARE (HCC, n = 44; mCRC, n = 20; CCA, n = 6). Safety and toxicity were assessed using the National Cancer Institute Common Terminology Criteria. Treatment response was evaluated every 3 months on imaging studies using Response Evaluation Criteria in Solid Tumors (RECIST) or mRECIST criteria. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. The median delivered dose was 1.6 GBq, with SIR-Spheres® or TheraSphere® microspheres. TARE-related grade 3 adverse events affected 17.1% of patients. Median follow-up was 32.1 months. Median progression-free survival was 5.6 months and median overall time from TARE to death was 16.1 months and was significantly shorter in men. Progression-free survival was significantly longer in women (HR, 0.49; 95%CI, 0.26-0.90; p = 0.031). Risk of death or progression increased with the number of systemic chemotherapy lines. TARE can be safe and effective in patients with intermediate- or advanced-stage HCC, CCA, or mCRC refractory or intolerant to appropriate treatments.

Performance Evaluation and Compatibility Studies of a Compact Preclinical Scanner for Simultaneous PET/MR Imaging at 7 Tesla.

We present the design and performance of a new compact preclinical system combining positron emission tomography (PET) and magnetic resonance imaging (MRI) for simultaneous scans. The PET contains sixteen SiPM-based detector heads arranged in two octagons and covers an axial field of view (FOV) of 102.5 mm. Depth of interaction effects and detector's temperature variations are compensated by the system. The PET is integrated in a dry magnet operating at 7 T. PET and MRI characteristics were assessed complying with international standards and interferences between both subsystems during simultaneous scans were addressed. For the rat size phantom, the peak noise equivalent count rates (NECR) were 96.4 kcps at 30.2 MBq and 132.3 kcps at 28.4 MBq respectively with and without RF coil. For mouse, the peak NECR was 300.0 kcps at 34.5 MBq and 426.9 kcps at 34.3 MBq respectively with and without coil. At the axial centre of the FOV, spatial resolutions expressed as full width at half maximum / full width at tenth maximum (FWHM/FWTM) ranged from 1.69/3.19 mm to 2.39/4.87 mm. The peak absolute sensitivity obtained with a 250-750 keV energy window was 7.5% with coil and 7.9% without coil. Spill over ratios of the NEMA NU4-2008 image quality (NEMA-IQ) phantom ranged from 0.25 to 0.96 and the percentage of non-uniformity was 5.7%. The image count versus activity was linear up to 40 MBq. The principal magnetic field variation was 0.03 ppm/mm over 40 mm. The qualitative and quantitative aspects of data were preserved during simultaneous scans.

FDG PET/CT in a Pregnant Woman With Breast Cancer.

This 37-year-old woman was diagnosed with breast cancer during pregnancy. After multidisciplinary meeting, she was referred to our department for an FDG PET/CT for staging, and chemotherapy with weekly infusion of paclitaxel was initiated before childbirth. We estimated the fetal dose from the PET/CT procedure, and our results show that, if deemed necessary, this examination can reasonably be performed during pregnancy. The patient gave birth vaginally at term to an apparently healthy girl.

Biological correlates of tumor perfusion and its heterogeneity in newly diagnosed breast cancer using dynamic first-pass 18F-FDG PET/CT.

PURPOSE: The aim of this prospective study is to analyze the global tumor blood flow (BF) and its heterogeneity in newly diagnosed breast cancer (BC) according to tumor biological characteristics and molecular subtypes. These perfusion parameters were compared to those classically derived from metabolic studies to investigate links between perfusion and metabolism. METHODS: Two hundred seventeen newly diagnosed BC patients underwent a 18F-FDG PET/CT exam before any treatment. A 2-min dynamic acquisition, centered on the chest, was performed immediately after intravenous injection of 3 MBq/kg of 18F-FDG, followed by a two-step static acquisition 90 min later. Tumor BF was calculated (in ml/min/g) using a single compartment kinetic model. In addition to standard PET parameters, texture features (TF) describing the heterogeneity of tumor perfusion and metabolism were extracted. Patients were divided into three groups: Luminal (HR+/HER2-), HER2 (HER2+), and TN (HR-/HER2-). Global and TF parameters of BF and metabolism were compared in different groups of patients according to tumor biological characteristics. RESULTS: Tumors with lymph node involvement showed a higher perfusion, whereas no significant differences in SUV_max or SUV_mean were reported. TN tumors had a higher metabolic activity than HER2 and luminal tumors but no significant differences in global BF values were noted. HER2 tumors exhibited a larger tumor heterogeneity of both perfusion and metabolism compared to luminal and TN tumors. Heterogeneity of perfusion appeared well correlated to that of metabolism. CONCLUSIONS: The study of breast cancer perfusion shows a higher BF in large tumors and in tumors with lymph node involvement, not paralleled by similar modifications in tumor global metabolism. In addition, the observed correlation between the perfusion heterogeneity and the metabolism heterogeneity suggests that tumor perfusion and consequently the process of tumor angiogenesis might be involved in the metabolism heterogeneity previously shown in BC.

Innovative Magnetic Nanoparticles for PET/MRI Bimodal Imaging.

Superparamagnetic iron oxide nanoparticles were developed as positron emission tomography (PET) and magnetic resonance imaging (MRI) bimodal imaging agents. These nanoparticles (NPs), with a specific nanoflower morphology, were first synthesized and simultaneously functionalized with 3,4-dihydroxy-l-phenylalanine (LDOPA) under continuous hydrothermal conditions. The resulting NPs exhibited a low hydrodynamic size of 90 ± 2 nm. The functional groups of LDOPA (-NH2 and -COOH) were successfully used for the grafting of molecules of interest in a second step. The nanostructures were modified by poly(ethylene glycol) (PEG) and a new macrocyclic chelator MANOTA for further 64Cu radiolabeling for PET imaging. The functionalized NPs showed promising bimodal (PET and MRI) imaging capability with high r 2 and r 2* (T 2 and T 2* relaxivities) values and good stability. They were mainly uptaken from liver and kidneys. No cytotoxicity effect was observed. These NPs appear as a good candidate for bimodal tracers in PET/MRI.

Modular Assembly of Multimodal Imaging Agents through an Inverse Electron Demand Diels-Alder Reaction.

The combination of two imaging probes on the same biomolecule gives access to targeted bimodal imaging agents that can provide more accurate diagnosis, complementary information, or that may be used in different applications, such as nuclear imaging and fluorescence guided surgery. In this study, we demonstrate that dichlorotetrazine, a small, commercially available compound, can be used as a modular platform to easily assemble various imaging probes. Doubly labeled tetrazines can then be conjugated to a protein through a biorthogonal IEDDA reaction. A series of difunctionalized tetrazine compounds containing various chelating agents and fluorescent dyes was synthesized. As a proof of concept, one of these bimodal probes was conjugated to trastuzumab, previously modified with a constrained alkyne group, and the resulting dual-labeled antibody was evaluated in a mouse model, bearing a HER2-positive tumor. A significant uptake into tumor tissues was observed in vivo, by both SPECT-CT and fluorescence imaging, and confirmed ex vivo in biodistribution studies.

Functionalization of theranostic AGuIX® nanoparticles for PET/MRI/optical imaging.

A novel trifunctional imaging probe containing a chelator of radiometal for PET, a NIR heptamethine cyanine dye, and a bioconjugatable handle, has been grafted onto AGuIX® nanoparticles via a Michael addition reaction. The resulting functionalized nanoparticles have been fully characterized, radiolabelled with 64Cu, and evaluated in a mice TSA tumor model using multimodal (PET/MRI/optical) imaging.

Functionalization of Gadolinium Chelates Silica Nanoparticle through Silane Chemistry for Simultaneous MRI/64Cu PET Imaging.

Multimodal nanoprobes are highly demanded for biomedical imaging applications to enhance the reliability of the diagnostic results. Among different types of nano-objects, ultrasmall silica gadolinium nanoparticle (SiGdNP) appears as a safe, effective, and versatile platform for this purpose. In this study, a new method to functionalize SiGdNP based on silane chemistry has been reported. Two types of chelating silanes (APTES-DOTAGA and APTES-NODAGA) have been synthesized and grafted on SiGdNP by a simple one-step protocol. This functionalization strategy requires no other reactants or catalyzers and does not compromise the ultrasmall size of the particles. NODAGA-functionalized particle has been labeled with 64Cu isotope and injected intravenously to mice bearing TS/A carcinoma tumor for biodistribution study to demonstrate its potential as a bimodal MRI/PET imaging agent. A fully integrated MRI/PET system was used to simultaneously monitor the distribution of the particle. The results showed that the functionalized particle maintained properties of a renal clearable NP which could rapidly escape through kidneys and had low retention in other organs, especially liver, even though its accumulation in the tumor was modest.

FDG PET/CT for prognostic stratification of patients with metastatic breast cancer treated with first line systemic therapy: Comparison of EORTC criteria and PERCIST.

AIM: Evaluate response and predict prognosis of patients with newly diagnosed metastatic breast cancer treated with first line systemic therapy using European Organization for Research and Treatment of Cancer (EORTC) criteria and PET Response Criteria in solid Tumours (PERCIST). METHODS: From December 2006 to August 2013, 57 women with newly diagnosed metastatic breast cancer were retrospectively evaluated. FDG-PET/CT was performed within one month before treatment and repeated after at least 3 cycles of treatment. Metabolic response evaluation was evaluated by two readers according to both EORTC criteria and PERCIST, classifying the patients into 4 response groups: complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD). RESULTS: With EORTC criteria, 22 patients had CMR, 17 PMR, 6 SMD and 12 PMD. With PERCIST, 20 patients had CMR, 15 PMR, 10 SMD and 12 PMD. There was agreement between EORTC and PERCIST in 84% of the patients. By log-rank analysis, metabolic response evaluated with both EORTC criteria and PERCIST was able to predict overall survival (p = 0.028 and 0.002 respectively). CMR patient group had longer median OS than patients in the combined PMR+SMD+PMD group (60 vs 26 months both with EORTC and PERCIST; p = 0.009 and 0.006 respectively). By multivariate analysis, CMR either with EORTC or PERCIST remained an independent predictor of survival. CONCLUSION: Metabolic response evaluation with EORTC criteria and PERCIST gave similar prognostic stratification for metastatic breast cancer treated with a first line of systemic therapy.

Automatic deformable PET/MRI registration for preclinical studies based on B-splines and non-linear intensity transformation.

PET images deliver functional data, whereas MRI images provide anatomical information. Merging the complementary information from these two modalities is helpful in oncology. Alignment of PET/MRI images requires the use of multi-modal registration methods. Most of existing PET/MRI registration methods have been developed for humans and few works have been performed for small animal images. We proposed an automatic tool allowing PET/MRI registration for pre-clinical study based on a two-level hierarchical approach. First, we applied a non-linear intensity transformation to the PET volume to enhance. The global deformation is modeled by an affine transformation initialized by a principal component analysis. A free-form deformation based on B-splines is then used to describe local deformations. Normalized mutual information is used as voxel-based similarity measure. To validate our method, CT images acquired simultaneously with the PET on tumor-bearing mice were used. Results showed that the proposed algorithm outperformed affine and deformable registration techniques without PET intensity transformation with an average error of 0.72 ± 0.44 mm. The optimization time was reduced by 23% due to the introduction of robust initialization. In this paper, an automatic deformable PET-MRI registration algorithm for small animals is detailed and validated. Graphical abstract ᅟ.

Nuclear Imaging Study of the Pharmacodynamic Effects of Debio 1143, an Antagonist of Multiple Inhibitor of Apoptosis Proteins (IAPs), in a Triple-Negative Breast Cancer Model.

Background: Debio 1143, a potent orally available SMAC mimetic, targets inhibitors of apoptosis proteins (IAPs) members and is currently in clinical trials. In this study, nuclear imaging evaluated the effects of Debio 1143 on tumor cell death and metabolism in a triple-negative breast cancer (TNBC) cell line (MDA-MB-231)-based animal model. Methods: Apoptosis induced by Debio 1143 was assessed by FACS (caspase-3, annexin 5 (A5)), binding of 99mTc-HYNIC-Annexin V, and a cell proliferation assay. 99mTc-HYNIC-Annexin V SPECT and [18F]-FDG PET were also performed in mice xenografted with MDA-MB-231 cells. Results: Debio 1143 induced early apoptosis both in vitro and in vivo 6 h after treatment. Debio 1143 inhibited tumor growth, which was associated with a decreased tumor [18F]-FDG uptake when measured during treatment. Conclusions: This imaging study combining SPECT and PET showed the early proapoptotic effects of Debio 1143 resulting in a robust antitumor activity in a preclinical TNBC model. These imaging biomarkers represent valuable noninvasive tools for translational and clinical research in TNBC.

18F-Choline Positron Emission Tomography/Computed Tomography and Multiparametric Magnetic Resonance Imaging for the Detection of Early Local Recurrence of Prostate Cancer Initially Treated by Radiation Therapy: Comparison With Systematic 3-Dimensional Transperineal Mapping Biopsy.

PURPOSE: To compare the diagnostic performance of 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT), multiparametric prostate magnetic resonance imaging (mpMRI), and a combination of both techniques for the detection of local recurrence of prostate cancer initially treated by radiation therapy. METHODS AND MATERIALS: This was a retrospective, single-institution study of 32 patients with suspected prostate cancer recurrence who underwent both FCH-PET/CT and 3T mpMRI within 3 months of one another for the detection of recurrence. All included patients had to be cleared for metastatic recurrence. The reference procedure was systematic 3-dimensional (3D)-transperineal prostate biopsy for the final assessment of local recurrence. Both imaging modalities were analyzed by 2 experienced readers blinded to clinical data. The analysis was made per-patient and per-segment using a 4-segment model. RESULTS: The median prostate-specific antigen value at the time of imaging was 2.92 ng/mL. The mean prostate-specific antigen doubling time was 14 months. Of the 32 patients, 31 had a positive 3D-transperineal mapping biopsy for a local relapse. On a patient-based analysis, the detection rate was 71% (22 of 31) for mpMRI and 74% (23 of 31) for FCH-PET/CT. On a segment-based analysis, the sensitivity and specificity were, respectively, 32% and 87% for mpMRI, 34% and 87% for FCH-PET/CT, and 43% and 83% for the combined analysis of both techniques. Accuracy was 64%, 65%, and 66%, respectively. The interobserver agreement was κ = 0.92 for FCH-PET/CT and κ = 0.74 for mpMRI. CONCLUSIONS: Both mpMRI and FCH-PET/CT show limited sensitivity but good specificity for the detection of local cancer recurrence after radiation therapy, when compared with 3D-transperineal mapping biopsy. Prostate biopsy still seems to be mandatory to diagnose local relapse and select patients who could benefit from local salvage therapy.