Prognostic value of visual IMPeTUs criteria and metabolic tumor burden at baseline [18F]FDG PET/CT in patients with newly diagnosed multiple myeloma.

BACKGROUND: 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography combined with low-dose computed tomography (PET/CT) can be used at diagnosis to identify myeloma-defining events and also provides prognostic factors. The aim of this study was to assess the prognostic significance of baseline [18F]FDG PET/CT visual IMPeTUs (Italian myeloma criteria for PET Use)-based parameters and/or total metabolic tumor volume (TMTV) in a single-center population of patients with newly diagnosed multiple myeloma (NDMM) eligible for transplantation. METHODS: Patients with MM who underwent a baseline [18F]FDG PET/CT were retrospectively selected from a large internal database of the University Hospital of Liege (Liege, Belgium). Initially, all PET/CT images were visually analyzed using IMPeTUs criteria, followed by delineation of TMTV using a semi-automatic lesion delineation workflow, including [18F]FDG-positive MM focal lesions (FL) with an absolute SUV threshold set at 4.0. In a first step, to ensure PET/CT scans accurate reporting, the agreement between two nuclear medicine physicians with distinct experience was assessed. In the second step, univariable and multivariable analyses were conducted to determine the prognostic significance of [18F]FDG PET/CT parameters on progression free survival (PFS) and overall survival (OS), respectively. RESULTS: A total of 40 patients with NDMM were included in the study. The observers agreement in the analysis [18F]FDG PET/CT images was substantial for the presence of spine FL, extra spine FL, at least one fracture and paramedullary disease (Cohen's kappa 0.79, 0.87, 0.75 and 0.64, respectively). For the presence of skull FL and extramedullary disease the agreement was moderate (Cohen's kappa 0.56 and 0.53, respectively). Among [18F]FDG PET/CT parameters, a high number of delineated volumes of interest (VOI) using the SUV4.0 threshold was the only independent prognostic factor associated with PFS [HR (95% CI): 1.03 (1.004-1.05), P = 0.019] while a high number of FL (n > 10; F group 4) was the only independent prognostic factor associated with OS [HR (95% CI): 19.10 (1.90-191.95), P = 0.01]. CONCLUSION: Our work confirms the reproducibility IMPeTUs criteria. Furthermore, it demonstrates that a high number of FL (n > 10; IMPeTUs F group 4), reflecting a high [18F]FDG-avid tumor burden, is an independent prognostic factor for OS. The prognostic value of the TMTV delineated using a SUV4.0 threshold was not significant. Nevertheless, the count of delineated [18F]FDG-avid lesions VOI using a SUV4.0 threshold was an independent prognostic factor for PFS.

[PET/CT in radiotherapy : indications and potential applications]. / TEP/TDM en radiothérapie : indications et perspectives.

Functional imaging, including positron emission tomography combined with computed tomography (PET/CT), allows the evaluation of numerous biological properties that could be considered at all steps of the therapeutic management of patients treated with radiotherapy. Indeed, it enables better initial staging of the disease, and some parameters may also be used as predictive biomarkers for treatment response, allowing better selection of patients eligible for radiotherapy. It may also improve the definition of target volumes with the aim of dose escalations by dose-painting. Finally, it could be useful during the follow-up to assess response to treatment. In this review, we report how functional imaging is integrated at the present time during the radiotherapy procedure, and what are its potential future contributions.

L'imagerie fonctionnelle, dont la tomographie par émission de positons couplée à la tomodensitométrie (TEP/TDM), permet l'évaluation de nombreuses propriétés biologiques qui pourraient être prises en compte à toutes les étapes de la prise en charge des patients traités par radiothérapie. En effet, elle permet une meilleure stadification initiale de la maladie, et certains paramètres peuvent également être utilisés comme biomarqueurs prédictifs de la réponse au traitement, permettant ainsi une meilleure sélection des patients éligibles à la radiothérapie. Elle peut également améliorer la définition des volumes cibles dans le but d'escalader la dose par dose-painting. Enfin, elle pourrait être utile lors du suivi pour évaluer la réponse au traitement. Dans cette revue, nous rapportons comment l'imagerie fonctionnelle est intégrée, à l'heure actuelle, au cours d'un traitement par radiothérapie, et nous discutons quelles sont ses futures contributions potentielles dans les principales localisations tumorales où la radiothérapie est recommandée.

Walk-through flat panel total-body PET: a patient-centered design for high throughput imaging at lower cost using DOI-capable high-resolution monolithic detectors.

PURPOSE: Long axial field-of-view (LAFOV) systems have a much higher sensitivity than standard axial field-of-view (SAFOV) PET systems for imaging the torso or full body, which allows faster and/or lower dose imaging. Despite its very high sensitivity, current total-body PET (TB-PET) throughput is limited by patient handling (positioning on the bed) and often a shortage of available personnel. This factor, combined with high system costs, makes it hard to justify the implementation of these systems for many academic and nearly all routine nuclear medicine departments. We, therefore, propose a novel, cost-effective, dual flat panel TB-PET system for patients in upright standing positions to avoid the time-consuming positioning on a PET-CT table; the walk-through (WT) TB-PET. We describe a patient-centered, flat panel PET design that offers very efficient patient throughput and uses monolithic detectors (with BGO or LYSO) with depth-of-interaction (DOI) capabilities and high intrinsic spatial resolution. We compare system sensitivity, component costs, and patient throughput of the proposed WT-TB-PET to a SAFOV (= 26 cm) and a LAFOV (= 106 cm) LSO PET systems. METHODS: Patient width, height (= top head to start of thighs) and depth (= distance from the bed to front of patient) were derived from 40 randomly selected PET-CT scans to define the design dimensions of the WT-TB-PET. We compare this new PET system to the commercially available Siemens Biograph Vision 600 (SAFOV) and Siemens Quadra (LAFOV) PET-CT in terms of component costs, system sensitivity, and patient throughput. System cost comparison was based on estimating the cost of the two main components in the PET system (Silicon Photomultipliers (SiPMs) and scintillators). Sensitivity values were determined using Gate Monte Carlo simulations. Patient throughput times (including CT and scout scan, patient positioning on bed and transfer) were recorded for 1 day on a Siemens Vision 600 PET. These timing values were then used to estimate the expected patient throughput (assuming an equal patient radiotracer injected activity to patients and considering differences in system sensitivity and time-of-flight information) for WT-TB-PET, SAFOV and LAFOV PET. RESULTS: The WT-TB-PET is composed of two flat panels; each is 70 cm wide and 106 cm high, with a 50-cm gap between both panels. These design dimensions were justified by the patient sizes measured from the 40 random PET-CT scans. Each panel consists of 14 × 20 monolithic BGO detector blocks that are 50 × 50 × 16 mm in size and are coupled to a readout with 6 × 6 mm SiPMs arrays. For the WT-TB-PET, the detector surface is reduced by a factor of 1.9 and the scintillator volume by a factor of 2.2 compared to LAFOV PET systems, while demonstrating comparable sensitivity and much better uniform spatial resolution (< 2 mm in all directions over the FOV). The estimated component cost for the WT-TB-PET is 3.3 × lower than that of a 106 cm LAFOV system and only 20% higher than the PET component costs of a SAFOV. The estimated maximum number of patients scanned on a standard 8-h working day increases from 28 (for SAFOV) to 53-60 (for LAFOV in limited/full acceptance) to 87 (for the WT-TB-PET). By scanning faster (more patients), the amount of ordered activity per patient can be reduced drastically: the WT-TB-PET requires 66% less ordered activity per patient than a SAFOV. CONCLUSIONS: We propose a monolithic BGO or LYSO-based WT-TB-PET system with DOI measurements that departs from the classical patient positioning on a table and allows patients to stand upright between two flat panels. The WT-TB-PET system provides a solution to achieve a much lower cost TB-PET approaching the cost of a SAFOV system. High patient throughput is increased by fast patient positioning between two vertical flat panel detectors of high sensitivity. High spatial resolution (< 2 mm) uniform over the FOV is obtained by using DOI-capable monolithic scintillators.

European Association of Nuclear Medicine (EANM) Focus 4 consensus recommendations: molecular imaging and therapy in haematological tumours.

Given the paucity of high-certainty evidence, and differences in opinion on the use of nuclear medicine for hematological malignancies, we embarked on a consensus process involving key experts in this area. We aimed to assess consensus within a panel of experts on issues related to patient eligibility, imaging techniques, staging and response assessment, follow-up, and treatment decision-making, and to provide interim guidance by our expert consensus. We used a three-stage consensus process. First, we systematically reviewed and appraised the quality of existing evidence. Second, we generated a list of 153 statements based on the literature review to be agreed or disagreed with, with an additional statement added after the first round. Third, the 154 statements were scored by a panel of 26 experts purposively sampled from authors of published research on haematological tumours on a 1 (strongly disagree) to 9 (strongly agree) Likert scale in a two-round electronic Delphi review. The RAND and University of California Los Angeles appropriateness method was used for analysis. Between one and 14 systematic reviews were identified on each topic. All were rated as low to moderate quality. After two rounds of voting, there was consensus on 139 (90%) of 154 of the statements. There was consensus on most statements concerning the use of PET in non-Hodgkin and Hodgkin lymphoma. In multiple myeloma, more studies are required to define the optimal sequence for treatment assessment. Furthermore, nuclear medicine physicians and haematologists are awaiting consistent literature to introduce volumetric parameters, artificial intelligence, machine learning, and radiomics into routine practice.

Radiotheranostic Agents in Hematological Malignancies.

Radioimmunotherapy (RIT) is a cancer treatment that combines radiation therapy with tumor-directed monoclonal antibodies (Abs). Although RIT had been introduced for the treatment of CD20 positive non-Hodgkin lymphoma decades ago, it never found a broad clinical application. In recent years, researchers have developed theranostic agents based on Ab fragments or small Ab mimetics such as peptides, affibodies or single-chain Abs with improved tumor-targeting capacities. Theranostics combine diagnostic and therapeutic capabilities into a single pharmaceutical agent; this dual application can be easily achieved after conjugation to radionuclides. The past decade has seen a trend to increased specificity, fastened pharmacokinetics, and personalized medicine. In this review, we discuss the different strategies introduced for the noninvasive detection and treatment of hematological malignancies by radiopharmaceuticals. We also discuss the future applications of these radiotheranostic agents.

Facts and Fictions About [18F]FDG versus Other Tracers in Managing Patients with Brain Tumors: It Is Time to Rectify the Ongoing Misconceptions.

MRI is the first-choice imaging technique for brain tumors. Positron emission tomography can be combined together with multiparametric MRI to increase diagnostic confidence. Radiolabeled amino acids have gained wide clinical acceptance. The reported pooled specificity of [18F]FDG positron emission tomography is high and [18F]FDG might still be the first-choice positron emission tomography tracer in cases of World Health Organization grade 3 to 4 gliomas or [18F]FDG-avid tumors, avoiding the use of more expensive and less available radiolabeled amino acids. The present review discusses the additional value of positron emission tomography with a focus on [18F]FDG and radiolabeled amino acids.

Distinction of Lymphoma from Sarcoidosis on 18F-FDG PET/CT: Evaluation of Radiomics-Feature-Guided Machine Learning Versus Human Reader Performance.

Sarcoidosis and lymphoma often share common features on 18F-FDG PET/CT, such as intense hypermetabolic lesions in lymph nodes and multiple organs. We aimed at developing and validating radiomics signatures to differentiate sarcoidosis from Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL). Methods: We retrospectively collected 420 patients (169 sarcoidosis, 140 HL, and 111 DLBCL) who underwent pretreatment 18F-FDG PET/CT at the University Hospital of Liege. The studies were randomly distributed to 4 physicians, who gave their diagnostic suggestion among the 3 diseases. The individual and pooled performance of the physicians was then calculated. Interobserver variability was evaluated using a sample of 34 studies interpreted by all physicians. Volumes of interest were delineated over the lesions and the liver using MIM software, and 215 radiomics features were extracted using the RadiomiX Toolbox. Models were developed combining clinical data (age, sex, and weight) and radiomics (original and tumor-to-liver TLR radiomics), with 7 different feature selection approaches and 4 different machine-learning (ML) classifiers, to differentiate sarcoidosis and lymphomas on both lesion-based and patient-based approaches. Results: For identifying lymphoma versus sarcoidosis, physicians' pooled sensitivity, specificity, area under the receiver-operating-characteristic curve (AUC), and accuracy were 0.99 (95% CI, 0.97-1.00), 0.75 (95% CI, 0.68-0.81), 0.87 (95% CI, 0.84-0.90), and 89.3%, respectively, whereas for identifying HL in the tumor population, it was 0.58 (95% CI, 0.49-0.66), 0.82 (95% CI, 0.74-0.89), 0.70 (95% CI, 0.64-0.75) and 68.5%, respectively. Moderate agreement was found among observers for the diagnosis of lymphoma versus sarcoidosis and HL versus DLBCL, with Fleiss κ-values of 0.66 (95% CI, 0.45-0.87) and 0.69 (95% CI, 0.45-0.93), respectively. The best ML models for identifying lymphoma versus sarcoidosis showed an AUC of 0.94 (95% CI, 0.93-0.95) and 0.85 (95% CI, 0.82-0.88) in lesion- and patient-based approaches, respectively, using TLR radiomics (plus age for the second). To differentiate HL from DLBCL, we obtained an AUC of 0.95 (95% CI, 0.93-0.96) in the lesion-based approach using TLR radiomics and 0.86 (95% CI, 0.80-0.91) in the patient-based approach using original radiomics and age. Conclusion: Characterization of sarcoidosis and lymphoma lesions is feasible using ML and radiomics, with very good to excellent performance, equivalent to or better than that of physicians, who showed significant interobserver variability in their assessment.

Using 68Ga-PSMA-11 PET/CT for Therapy Response Assessment in Patients with Metastatic Castration-Resistant Prostate Cancer: Application of EAU/EANM Recommendations in Clinical Practice.

For patients with metastatic castration-resistant prostate cancer (mCRPC), no reliable biomarkers for predicting therapeutic response or assisting in treatment selection and sequencing are currently available. Using the recent European Association of Urology and European Association of Nuclear Medicine recommendations, we aimed to compare response assessment between prostate-specific membrane antigen (PSMA) PET/CT and conventional imaging in mCRPC patients starting first-line treatment with a novel hormonal agent (NHA) and to perform a sequential comparative analysis of PSMA PET/CT-derived parameters after 4 and 12 wk of therapy. Methods: Data from 18 mCRPC patients who started NHA treatment and underwent 68Ga-PSMA-11 PET/CT before therapy initiation (baseline), at week 4 (W4), and at week 12 (W12) in addition to conventional imaging (bone scintigraphy, CT) at baseline and W12 were retrospectively included. PET/CT images were quantitatively analyzed for maximum and mean SUV and total PSMA ligand-positive lesions. Comparative analysis of PET/CT-derived parameters was performed, and patients were classified as having nonprogressive disease or progressive disease (PD) according to 68Ga-PSMA-11 PET/CT, prostate-specific antigen, and conventional imaging criteria. Results: Treatment response was evaluable by 68Ga-PSMA-11 PET/CT in 16 of 18 patients (89%) and by conventional imaging in 11 of 18 patients (61%). Five of 16 patients classified as having PD by 68Ga-PSMA-11 PET/CT at W12 had already met progression criteria at W4, and substantial agreement was observed between W4 and W12 (κ, 0.74) 68Ga-PSMA-11 PET/CT results. Nonetheless, 2 of 16 patients (13%) were incorrectly classified as having PD because of a flare phenomenon on PSMA PET/CT that disappeared at W12. Conclusion: Volumetric assessments of 68Ga-PSMA-11 PET/CT imaging can improve response evaluation in NHA-treated patients with mCRPC. Although early response assessments at W4 need to be approached with caution because of flare, 68Ga-PSMA-11 PET/CT imaging at W4 and W12 revealed substantial agreement in therapy response assessments; these findings warrant further investigation to distinguish PD from flare at W4 and help improve the understanding of resistance to therapy.

Cemiplimab for Cisplatin Resistant Metastatic Penile Cancer.

We report on a 75-year old man who presented with metastatic, squamous-cell carcinoma (SCC) of the penis whose disease had progressed after radiotherapy (RT) and cisplatin-based chemotherapy (CT). A strong PD-L1 expression as well as a CDKN2A mutation was documented, and he was given cemiplimab every 3 weeks at time of disease progression. Complete response (CR) was demonstrated after 10 cycles, and no toxicity was reported. However, this treatment was stopped after 13 cycles when the patient developed moderate severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pneumonitis which required a 2-week hospitalization for oxygen support. Six months later, he remains in CR. To our knowledge, this is the first demonstration of a CR with cemiplimab in a metastatic penile SCC patient previously treated with CT and RT for relapse. Furthermore, the patient remains disease-free despite cemiplimab was withdrawn due to SARS-CoV-2 pneumonitis.

Toward diagnostic relevance of the αVß5, αVß3, and αVß6 integrins in OA: expression within human cartilage and spinal osteophytes.

We previously reported 18FPRGD2 uptake by the coxofemoral lining, intervertebral discs and facet joint osteophytes in OA using PET/SCAN imaging. However, the molecular mechanism by which the PRGD2 tracer interacts with joint tissues and osteophytes in OA remains unclear. As PRGD2 ligands are expected to belong to the RGD-specific integrin family, the purpose of this study was (i) to determine which integrin complexes display the highest affinity for PRGD2-based ligands, (ii) to analyze integrin expression in relevant tissues, and (iii) to test integrin regulation in chondrocytes using OA-related stimuli to increase the levels of fibrosis and ossification markers. To this end, the affinity of PRGD2-based ligands for five heterodimeric integrins was measured by competition with 125I-echistatin. In situ analyses were performed in human normal vs. OA cartilage and spinal osteophytes. Osteophytes were characterized by (immuno-)histological staining. Integrin subunit expression was tested in chondrocytes undergoing dedifferentiation, osteogenic differentiation, and inflammatory stimulation. The integrins αVß5, αVß3, and αVß6 presented the highest affinity for PRGD2-based ligands. In situ, the expression of these integrins was significantly increased in OA compared to normal cartilage. Within osteophytes, the mean integrin expression score was significantly higher in blood vessels, fibrous areas, and cells from the bone lining than in osteocytes and cartilaginous zones. In vitro, the levels of integrin subunits were significantly increased during chondrocyte dedifferentiation (except for ß6), fibrosis, and osteogenic differentiation as well as under inflammatory stimuli. In conclusion, anatomical zones (such as OA cartilage, intervertebral discs, and facet joint osteophytes) previously reported to show PRGD2 ligand uptake in vivo expressed increased levels of αVß5, αVß3, and ß6 integrins, whose subunits are modulated in vitro by OA-associated conditions that increase fibrosis, inflammation, and osteogenic differentiation. These results suggest that the increased levels of integrins in OA compared to normal tissues favor PRGD2 uptake and might explain the molecular mechanism of OA imaging using the PRGD2-based ligand PET/CT.

Interobserver agreement of [68Ga]Ga-PSMA-11 PET/CT images interpretation in men with newly diagnosed prostate cancer.

BACKGROUND: Prostate-specific membrane antigen (PSMA) ligand PET/CT has already provided promising results in prostate cancer (PC) imaging, yet simple and reproductible reporting criteria are still lacking. This study aimed at retrospectively evaluating interobserver agreement of [68Ga]Ga-PSMA-11 PET/CT images interpretation according to PC molecular imaging standardized evaluation (PROMISE) criteria and reproducibility of PSMA reporting and data systems (RADS). METHODS: Forty-three patients with newly diagnosed, histologically proven intermediate- or high-risk PC, eligible for radical prostatectomy and who underwent [68Ga]Ga-PSMA-11 PET/CT before surgery were retrospectively included. Three nuclear medicine physicians (2 experienced and 1 resident) independently reviewed PET/CT images. Interpretation of [68Ga]Ga-PSMA-11 PET/CT images was based on PROMISE criteria including miTNM staging and lesions miPSMA expression score visual estimation and PSMA-RADS version 1.0 for a given scan. Readers' agreement was measured using Krippendorff's coefficients RESULTS: Agreement between observers was almost perfect (coefficient ≥ 0.81) for miM; it was substantial (coefficient ≥ 0.61) for the following criteria: miT, miN, PSMA-RADS, and miPSMA expression score of primary PC lesion and metastases. However, agreement was moderate (coefficient = 0.41-0.60) for miPSMA score of positive lymph nodes and for detection of PC primary lesion. CONCLUSION: Visual interpretation of [68Ga]Ga-PSMA-11 PET/CT images in patients with newly diagnosed PC in a clinical setting leads to at least substantial agreement for PROMISE criteria and PSMA-RADS classification except for PC primary lesion detection and for miPSMA expression scoring of positive lymph nodes that might have been hampered by the interindividual variability of reference organs PSMA expression.

Dual-tracer PET/CT scan after injection of combined [18 F]NaF and [18 F]FDG outperforms MRI in the detection of myeloma lesions.

The detection rates of whole-body combined [18 F]NaF/[18 F]FDG positron emission tomography combined with computed tomography (PET/CT), CT alone, whole-body magnetic resonance imaging (WB-MRI), and X-ray were prospectively studied in patients with treatment-requiring plasma cell disorders The detection rates of imaging techniques were compared, and focal lesions were classified according to their anatomic location. Twenty-six out of 30 initially included patients were assessable. The number of focal lesions detected in newly diagnosed patients (n = 13) and in relapsed patients (n = 13) were 296 and 234, respectively. The detection rate of PET/CT was significantly higher than those of WB-MRI (P < 0.05) and CT (P < 0.0001) both in patients with newly diagnosed and in those with relapsed multiple myeloma (MM). The X-ray detection rate was significantly lower than those of all other techniques, while CT detected more lesions compared with WB-MRI at diagnosis (P = 0.025). With regard to the infiltration patters, relapsed patients presented more diffuse patterns, and more focal lesions located in the limbs compared with newly diagnosed patients. In conclusion, the detection rate of [18 F]NaF/[18 F]FDG PET/CT was significantly higher than those of CT, MRI, and X-ray, while the detection rate of X-rays was significantly lower than those of all other imaging techniques except for focal lesions located in the skull.

Molecular mechanisms, current management and next generation therapy in myeloma bone disease.

Multiple myeloma (MM) bone disease is a major cause of morbidity and mortality in MM patients and persists even in patients in remission. This bone disease is caused by an uncoupling of bone remodeling, with increased osteoclast and decreased osteoblast activity and formation, culminating in lytic bone destruction. Bisphosphonates are the current standard of care but new therapies are needed. As the molecular mechanisms controlling MM bone disease are increasingly well understood, new therapeutic targets are extensively explored in the preclinical setting and initial clinical trials with novel compounds now show promising results. In this review, we will provide a comprehensive overview of the biology of MM bone disease, summarize its current clinical management and discuss preclinical and clinical data on next generation therapies.

A First Report on [18F]FPRGD2 PET/CT Imaging in Multiple Myeloma.

An observational study was set up to assess the feasibility of [18F]FPRGD2 PET/CT for imaging patients with multiple myeloma (MM) and to compare its detection rate with low dose CT alone and combined [18F]NaF/[18F]FDG PET/CT images. Four patients (2 newly diagnosed patients and 2 with relapsed MM) were included and underwent whole-body PET/CT after injection of [18F]FPRGD2. The obtained images were compared with results of low dose CT and already available results of a combined [18F]NaF/[18F]FDG PET/CT. In total, 81 focal lesions (FLs) were detected with PET/CT and an underlying bone destruction or fracture was seen in 72 (89%) or 8 (10%) FLs, respectively. Fewer FLs (54%) were detected by [18F]FPRGD2 PET/CT compared to low dose CT (98%) or [18F]NaF/[18F]FDG PET/CT (70%) and all FLs detected with [18F]FPRGD2 PET were associated with an underlying bone lesion. In one newly diagnosed patient, more [18F]FPRGD2 positive lesions were seen than [18F]NaF/[18F]FDG positive lesions. This study suggests that [18F]FPRGD2 PET/CT might be less useful for the detection of myeloma lesions in patients with advanced disease as all FLs with [18F]FPRGD2 uptake were already detected with CT alone.

A case of added value of 123I-mIBG SPECT/CT imaging in the diagnosis of a pheochromocytoma extending into the left adrenal vein.

We present the case of a 48-year-old patient with a left adrenal incidentaloma found on computed tomography (CT) for which the diagnosis of pheochromocytoma was confirmed by a 24-hour urinary dosage of norepinephrine. The 123I-mIBG scintigraphy showed a high uptake of 123I-mIBG in the left adrenal gland and, additionally, the single photon emission computed tomography combined with a low-dose CT (SPECT/CT) suggested the extension into the adrenal vein. The diagnostic CT and magnetic resonance images agreed with these findings and the subsequent surgery confirmed the vascular invasion.

Multimodality imaging assessment of the deleterious role of the intraluminal thrombus on the growth of abdominal aortic aneurysm in a rat model.

OBJECTIVES: To evaluate imaging changes occurring in a rat model of elastase-induced abdominal aortic aneurysm (AAA), with emphasis on the intraluminal thrombus (ILT) occurrence. METHODS: The post-induction growth of the AAA diameter was characterized using ultrasound in 22 rats. ILT was reported on 13 rats that underwent 14 magnetic resonance imaging (MRI) 2-18 days post-surgery, and on 10 rats that underwent 18 fluoro-deoxyglucose (FDG) positron emission tomography (PET)/microcomputed tomography examinations 2-27 days post-surgery. Logistic regressions were used to establish the evolution with time of AAA length, diameter, ILT thickness, volume, stratification, MRI and FDG PET signalling properties, and histological assessment of inflammatory infiltrates. RESULTS: All of the following significantly increased with time post-induction (p < 0.001): AAA length, AAA diameter, ILT maximal thickness, ILT volume, ILT iron content and related MRI signalling changes, quantitative uptake on FDG PET, and the magnitude of inflammatory infiltrates on histology. However, the aneurysm growth peak followed occurrence of ILT approximately 6 days after elastase infusion. CONCLUSION: Our model emphasizes that occurrence of ILT precedes AAA peak growth. Aneurysm growth is associated with increasing levels of iron, signalling properties changes in both MRI and FDG PET, relating to its biological activities. KEY POINTS: • ILT occurrence in AAA is associated with increasing FDG uptake and growth. • MRI signalling changes in ILT reflect activities such as haemorrhage and RBC trapping. • Monitoring ILT activities using MRI may require no exogenous contrast agent.

[(18)F]FPRGD2 PET/CT imaging of integrin αvß3 levels in patients with locally advanced rectal carcinoma.

PURPOSE: Our primary objective was to determine if [(18)F]FPRGD2 PET/CT performed at baseline and/or after chemoradiotherapy (CRT) could predict tumour regression grade (TRG) in locally advanced rectal cancer (LARC). Secondary objectives were to compare baseline [(18)F]FPRGD2 and [(18)F]FDG uptake, to evaluate the correlation between posttreatment [(18)F]FPRGD2 uptake and tumour microvessel density (MVD) and to determine if [(18)F]FPRGD2 and FDG PET/CT could predict disease-free survival. METHODS: Baseline [(18)F]FPRGD2 and FDG PET/CT were performed in 32 consecutive patients (23 men, 9 women; mean age 63 ± 8 years) with LARC before starting any therapy. A posttreatment [(18)F]FPRGD2 PET/CT scan was performed in 24 patients after the end of CRT (median interval 7 weeks, range 3 - 15 weeks) and before surgery (median interval 4 days, range 1 - 15 days). RESULTS: All LARC showed uptake of both [(18)F]FPRGD2 (SUVmax 5.4 ± 1.5, range 2.7 - 9) and FDG (SUVmax 16.5 ± 8, range 7.1 - 36.5). There was a moderate positive correlation between [(18)F]FPRGD2 and FDG SUVmax (Pearson's r = 0.49, p = 0.0026). There was a moderate negative correlation between baseline [(18)F]FPRGD2 SUVmax and the TRG (Spearman's r = -0.37, p = 0.037), and a [(18)F]FPRGD2 SUVmax of >5.6 identified all patients with a complete response (TRG 0; AUC 0.84, 95 % CI 0.68 - 1, p = 0.029). In the 24 patients who underwent a posttreatment [(18)F]FPRGD2 PET/CT scan the response index, calculated as [(SUVmax1 - SUVmax2)/SUVmax1] × 100 %, was not associated with TRG. Post-treatment [(18)F]FPRGD2 uptake was not correlated with tumour MVD. Neither [(18)F]FPRGD2 nor FDG uptake predicted disease-free survival. CONCLUSION: Baseline [(18)F]FPRGD2 uptake was correlated with the pathological response in patients with LARC treated with CRT. However, the specificity was too low to consider its clinical routine use.

¹8F-FPRGD2 PET/CT imaging of musculoskeletal disorders.

OBJECTIVE: This work reports on musculoskeletal uptake of ¹8F-FPRGD2, targeting the integrin αvß3, in patients who had undergone ¹8F-FPRGD2 positron emission tomography combined with computed tomography (PET/CT) for oncologic purposes. METHODS: Whole-body ¹8F-FPRGD2 PET/CT images of 62 cancer patients were retrospectively reviewed to detect foci of musculoskeletal ¹8F-FPRGD2 uptake. For 37 patients, a FDG PET/CT performed in clinical settings was available. In each joint with an abnormal uptake, the maximum standardized uptake value (SUVmax) was estimated. RESULTS: A total of 260 musculoskeletal foci of ¹8F-FPRGD2 uptake were detected. Most common sites of uptake were joints and discs (n = 160; 61.5%), entheses (osteotendinous and osteoligamentous junctions; n = 55; 21.2%) and recent fractures (n = 18; 6.9%). In addition, 27 (10.4%) miscellaneous foci were detected. Out of the 146 lesions for which a FDG PET was available, 63% showed both ¹8F-FPRGD2 and FDG uptake, 33.6% did not show FDG avidity and 3.4% showed only FDG uptake. The uptake intensity of the 92 lesions positive with ¹8F-FPRGD2 and FDG was similar with both radiopharmaceuticals, but the target-to-background (blood pool or muscle) ratios were significantly higher with ¹8F-FPRGD2 than with FDG (p < 0.0001). CONCLUSION: The ¹8F-FPRGD2 uptake in joints, spine degenerative diseases and tendons was highly prevalent in our population. Up to one-third of ¹8F-FPRGD2 foci showed no FDG uptake suggesting that ¹8F-FPRGD2 signal may not be related to inflammatory angiogenesis only.

18F-FPRGD2 PET/CT imaging of integrin αvß3 in renal carcinomas: correlation with histopathology.

UNLABELLED: This study aimed to correlate (18)F-FB-mini-PEG-E[c(RGDyK)](2) ((18)F-FPRGD2) uptake to integrin αvß3 expression and angiogenesis in renal tumors. METHODS: (18)F-FPRGD2 PET/CT was performed on 27 patients before surgical resection (median 4 d) of a renal mass. The (18)F-FPRGD2 uptake was compared with integrin αvß3, CD31, CD105, and Ki-67 using immunohistochemistry; with placental growth factor and vascular endothelial growth factor receptors 1 and 2 using reverse transcription polymerase chain reaction; and with vascular endothelial growth factor A isoforms using enzyme-linked immunosorbent assay. RESULTS: Overall, (18)F-FPRGD2 uptake significantly correlated (P < 0.0001) with integrin αvß3 expression in renal masses. However, it correlated only with integrin αvß3-positive vessels in the group of papillary carcinomas whereas it correlated with integrin αvß3 expression by tumor cells in the clear cell carcinoma group. CONCLUSION: (18)F-FPRGD2 uptake reflects the expression of integrin αvß3 in renal tumors but represents angiogenesis only when tumor cells do not express the integrin.