Ludovic Ferrer

Brain metastases or primary brain tumours had poor prognosis until the use of high dose radiotherapy. However, radionecrosis is a complex challenge in the post-radiotherapy management of these patients due to the difficulty of distinguishing this complication from local tumour recurrence. MRI alone has a variable specificity and sensibility, as does PET-CT imaging. We aimed to investigate the diagnostic performance of dual-phase ¹⁸F-FDG PET-mpMRI to distinguish cerebral radionecrosis from local tumour recurrence after cranial radiotherapy. A retrospective analysis was conducted between May 2021 and September 2022. Inclusion criteria encompassed patients with inconclusive MRI findings post-radiotherapy and history of cerebral radiotherapy for primary or metastatic brain lesions. Lesions are assessed qualitatively and semi-quantitatively. The gold standard to assess radionecrosis was histopathology or a composite criterion at three months. The study evaluated 24 lesions in 23 patients. Qualitative analysis yielded 85.7% sensitivity and 75% specificity. Semi-quantitative analysis, based on contralateral background noise, achieved 100% sensitivity and 50% specificity. Moreover, using contralateral frontal lobe background noise resulted in higher performances with 92% sensitivity and 63% specificity. Stratification by lesion type demonstrated 100% sensitivity and specificity rates for metastatic lesions. The diagnostic performance of dual-phase ¹⁸F-FDG PET-mpMRI shows promising results for metastatic lesions.

Purpose: Vaccination against coronavirus disease 2019 (COVID-19) is currently under worldwide deployment. The consequences of this vaccination can be seen in radiology and nuclear medicine explorations with visualization of axillary lymph nodes (LNs), as observed on ultrasonography, MRI, or ¹⁸F-FDG PET/CT. We aimed to evaluate on PET/CT the incidence of vaccine-related LNs and their characteristics after COVID-19 vaccination, using several radiopharmaceuticals different from ¹⁸F-FDG. Patients and Methods: Between February and July 2021, all consecutive patients undergoing a whole-body PET/CT for any indication using a different radiopharmaceutical from ¹⁸F-FDG were eligible for inclusion if they had received at least 1 dose of the COVID-19 vaccine. The radiopharmaceutical administered and vaccine type were recorded for each patient. The incidence of positive vaccine-related axillary and supraclavicular LNs on PET/CT was our primary finding, along with the nodes characteristics. Statistical analyses were performed for patients with prostate cancer (PCa) to determine certain interaction factors that were associated with the detection of vaccine-related LNs. Results: Of the 226 patients in our cohort study, 120 patients underwent an ¹⁸F-fluorocholine PET/CT, 79 a ⁶⁸Ga-PSMA-11 PET/CT, 6 an ¹⁸F-FDOPA PET/CT, and 21 a ⁶⁸Ga-DOTATOC PET/CT. A total of 67.3% of patients (152/226) received BNT162b2mRNA (Pfizer-BioNTech), 26.5% (60/226) ChAdOx1-S (AstraZeneca), 4.9% (11/226) mRNA-1273 (Moderna), and 1.3% (3/226) Ad26.COV2.S (Janssen). The incidence of positive vaccine-related axillary and supraclavicular LNs was 42.5% (51/120 patients) on PET/CT using ¹⁸F-fluorocholine and 12.7% (10/79 patients) with ⁶⁸Ga-PSMA-11. None of our patients undergoing ¹⁸F-FDOPA or ⁶⁸Ga-DOTATOC PET/CT presented any vaccine-related lymphadenopathy. Vaccine-related LNs were statistically associated with the nature of the radiopharmaceutical (P < 10⁻⁴), with the number of vaccine doses received (P = 0.041), with a short delay between vaccination and PET/CT realization (P < 10⁻⁵), and with a higher prostate-specific antigen level for patients with PCa (P = 0.032), but not with age or vaccine type. The vaccine-related nodes appeared in 85% of the cases, in the 30 days after vaccine injection, were limited in size and uptake, and were most often limited to the axilla level 1 area. Conclusions: Detecting positive LNs after COVID-19 vaccination is not an exclusive ¹⁸F-FDG PET/CT pattern but is common on ¹⁸F-fluorocholine and possible on ⁶⁸Ga-PSMA-11 PET/CT. Confronting PET/CT findings with clinical data (such as date and site of injection) seems essential in the current pandemic context, just as it does for the radiopharmaceuticals used in PCa to avoid PET/CT misinterpretation and incorrect patient treatment. For ¹⁸F-FDOPA or ⁶⁸Ga-DOTATOC PET/CT, this seems to have a lesser impact.

(1) Background: Stereotactic body radiotherapy (SBRT) for vertebral metastases (VM) allows the delivery of high radiation doses to tumors while sparing the spinal cord. We report a new approach to clinical target volume (CTV) delineation based on anti-carcinoembryonic antigen (CEA) positron emission tomography (pretargeted immuno-PET; “iPET”) in patients with metastatic breast cancer (BC) or medullary thyroid cancer (MTC). (2) Methods: All patients underwent iPET, spine magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT) using ¹⁸F-deoxyglucose (FDG) for BC or ¹⁸F-dihydroxy-phenylalanine (F-DOPA) for MTC. Vertebrae locations and vertebral segments of lesions were recorded and the impact on CTV delineation was evaluated. (3) Results: Forty-six VM eligible for SBRT following iPET were evaluated in eight patients (five BC, three MTC). Eighty-one vertebral segments were detected using MRI, 26 with FDG or F-DOPA PET/CT, and 70 using iPET. iPET was able to detect more lesions than MRI for vertebral bodies (44 vs. 34). iPET-based delineation modified MRI-based CTV in 70% (32/46) of cases. (4) Conclusion: iPET allows a precise mapping of affected VM segments, and adds complementary information to MRI in the definition of candidate volumes for VM SBRT. iPET may facilitate determining target volumes for treatment with stereotactic body radiotherapy in metastatic vertebral disease.

Due to the heterogeneity of tumour mass segmentation methods and lack of consensus, our study evaluated the prognostic value of pretherapeutic positron emission tomography with fluorodeoxyglucose (FDG-PET) metabolic parameters using different segmentation methods in patients with localized anal squamous cell carcinoma (SCC). Eighty-one patients with FDG-PET before radiochemotherapy were retrospectively analyzed. Semiquantitative data were measured with three fixed thresholds (35%, 41% and 50% of Maximum Standardized Uptake Value (SUVmax)) and four segmentation methods based on iterative approaches (Black, Adaptive, Nestle and Fitting). Metabolic volumes of primary anal tumour (P-MTV) and total tumour load (T-MTV: P-MTV+ lymph node MTV) were calculated. The primary endpoint was event-free survival (EFS). Seven multivariate models were created to compare FDG-PET tumour volumes prognostic impact. For all segmentation thresholds, PET metabolic volume parameters were independent prognostic factor and T-MTV variable was consistently better associated with EFS than P-MTV. Patient’s sex was an independent variable and significantly correlated with EFS. With fixed threshold segmentation methods, 35% of SUVmax threshold seemed better correlated with EFS and the best cut-off for discrimination between a low and high risk of event occurrence was 40 cm³. Determination of T-MTV by FDG-PET using fixed threshold segmentation is useful for predicting EFS for primary anal SCC. If these data are confirmed in larger studies, FDG-PET could contribute to individualized patient therapies.

Prostate cancer (PCa) pelvic radiotherapy fields are defined by guidelines that do not consider individual variations in lymphatic drainage. We examined the feasibility of personalized sentinel lymph node (SLN)-based pelvic irradiation in PCa. Among a SLN study of 202 patients, we retrospectively selected 57 patients with a high risk of lymph node involvement. Each single SLN clinical target volume (CTV) was individually segmented and pelvic CTVs were contoured according to Radiation Therapy Oncology Group (RTOG) guidelines. We simulated a radiotherapy plan delivering 46 Gy and calculated the dose received by each SLN. Among a total of 332 abdominal SLNs, 305 pelvic SLNs (beyond the aortic bifurcation) were contoured (mean 5.4/patient). Based on standard guidelines, CTV missed 67 SLNs (22%), mostly at the common iliac level (40 SLNs). The mean distance between iliac vessels and the SLN was 11mm, and despite a 15mm margin around the iliac vessels, 9% of SLNs were not encompassed by the CTV. Moreover, 42 SLNs (63%) did not receive 95% of the prescribed dose. Despite a consensus on contouring guidelines, a significant proportion of SLNs were not included in the pelvic CTV and did not receive the prescribed dose. A tailored approach based on individual SLN detection would avoid underdosing pelvic lymph nodes that potentially contain tumor cells.

Objectives. A phase I pretargeted radioimmunotherapy trial (EudractCT 200800603096) was designed in patients with metastatic lung cancer expressing carcinoembryonic antigen (CEA) to optimize bispecific antibody and labelled peptide doses, as well as the delay between their injections. Methods. Three cohorts of 3 patients received the anti-CEA x anti-histamine-succinyl-glycine (HSG) humanized trivalent bispecific antibody (TF2) and the IMP288 bivalent HSG-peptide. Patients underwent a pre-therapeutic imaging session S1 (44 or 88 nmol/m2 of TF2 followed by 4.4 nmol/m2, 185 MBq, of 111In-labelled IMP288), and, 1-2 weeks later, a therapy session S2 (240 or 480 nmol/m2 of TF2 followed by 24 nmol/m2, 1.1 GBq/m2, 177Lu-labeled IMP288). The pretargeting delay was 24 or 48 hours. The dose schedule was defined based on pre-clinical TF2 pharmacokinetic studies, on our previous clinical data using the previous anti-CEA pretargeting system and on clinical results observed in the first patients injected using the same system in the Netherlands. Results. TF2 pharmacokinetics (PK) was represented by a two-compartment model in which the central compartment volume was linearly dependent on the patient's surface area. PK were remarkably similar, with a clearance of 0.33 +/- 0.03 L/h per m2. 111In- and 177Lu-IMP288 PK were also well represented by a two-compartment model. IMP288 PK were faster (clearance 1.4 to 3.3 l/h). The central compartment volume was proportional to body surface area and IMP288clearance depended on the molar ratio of injected IMP288 to circulating TF2 at the time of IMP288 injection. Modelling of image quantification confirmed the dependence of IMP288 kinetics on circulating TF2, but tumour activity PK were variable. Organ absorbed doses were not significantly different in the 3 cohorts, but the tumour dose was significantly higher with the higher molar doses of TF2 (p < 0.002). S1 imaging predicted absorbed doses calculated in S2. Conclusion. The best dosing parameters corresponded to the shorter pretargeting delay and to the highest TF2 molar doses. S1 imaging session accurately predicted PK as well as absorbed doses of S2, thus potentially allowing for patient selection and dose optimization.

Despite the early theoretical prediction of the 0⁺-0⁺ transition of ⁹⁰Zr, ⁹⁰Y-PET underwent only recently a growing interest for the development of imaging radioembolization of liver tumors. The aim of this work was to determine the minimum detectable activity (MDA) of ⁹⁰Y by PET imaging and the impact of time-of-flight (TOF) reconstruction on detectability and quantitative accuracy according to the lesion size. The study was conducted using a Siemens Biograph® mCT with a 22 cm large axial field of view. An IEC torso-shaped phantom containing five coplanar spheres was uniformly filled to achieve sphere-to-background ratios of 40:1. The phantom was imaged nine times in 14 days over 30 min. Sinograms were reconstructed with and without TOF information. A contrast-to-noise ratio (CNR) index was calculated using the Rose criterion, taking partial volume effects into account. The impact of reconstruction parameters on quantification accuracy, detectability, and spatial localization of the signal was investigated. Finally, six patients with hepatocellular carcinoma and four patients included in different ⁹⁰Y-based radioimmunotherapy protocols were enrolled for the evaluation of the imaging parameters in a clinical situation. The highest CNR was achieved with one iteration for both TOF and non-TOF reconstructions. The MDA, however, was found to be lower with TOF than with non-TOF reconstruction. There was no gain by adding TOF information in terms of CNR for concentrations higher than 2 to 3 MBq mL⁻¹, except for infra-centimetric lesions. Recovered activity was highly underestimated when a single iteration or non-TOF reconstruction was used (10% to 150% less depending on the lesion size). The MDA was estimated at 1 MBq mL⁻¹ for a TOF reconstruction and infra-centimetric lesions. Images from patients treated with microspheres were clinically relevant, unlike those of patients who received systemic injections of ⁹⁰Y. Only one iteration and TOF were necessary to achieve an MDA around 1 MBq mL⁻¹ and the most accurate localization of lesions. For precise quantification, at least three iterations gave the best performance, using TOF reconstruction and keeping an MDA of roughly 1 MBq mL⁻¹. One and three iterations were mandatory to prevent false positive results for quantitative analysis of clinical data. http://IDRCB2011-A00043-38P101103