Among 19 pathologic 18F-FDG PET/CT performed with Discovery 710, SUVmax, and SUV mean were 4.1 (1.4C8.8) and 2.4 (0.8C4.9), respectively. with a median of 2 segments. S7 and S10 were the most involved segments with SUVmax 3.9 (1.3C8.8) and SUVmean 2.2 (0.7C4.9). Statistically significant difference (P?=?.02) was found with number of segment involved to characterize severe pneumopathy (average of PROTAC BET degrader-2 6.3 segments [2.5C11.5] vs 1.9 segments [0.5C8] for interstitial lung disease) but not with SUVmax, SUVmean, MTV, TLG (P?=?.14, 0.22, 0.22, and 0.17, respectively). The 18F-FDG PET/CT could highlight pulmonary everolimus side effects, with a typical imaging pattern: alveolar-interstitial opacities associated with moderate uptake, more or less extensive, mainly affecting the lower lobes. Rarely, a pseudotumoral aspect may be detected, corresponding to a pitfall. MTV or TLG showed a tendency to differentiate severe pneumopathy vs interstitial lung disease but no statistically significant differences was observed contrarily to the number of segments involved. Further studies are necessary to determine if the 18F-FDG PET/CT could early predict adverse effects of mTOR inhibitors. Keywords: everolimus, fluoro-deoxy-glucose, lung, positron emission tomography/computerized tomography, toxicity 1.?Introduction Novel targeted molecular therapies, among which Mamalian target of rapamycin (mTOR) inhibitors (including everolimus, sirolimus, temsirolimus, deforolimus) showed efficacy in oncology, especially in breast cancer when used alone or when combined with other therapies.[1,2] The everolimusCexemestane combination is indicated in advanced breast cancer treatment with positive hormonal receptor, HER2/neu negative, in case of recurrence or progression of the disease in postmenopausal women without symptomatic visceral disease and previously treated with a nonsteroidal aromatase inhibitor, because of improvement of progression-free survival.[3C5] One of the mechanisms involved in tumor resistance of first-line treatments (hormone therapy or immunotherapy) may be a permanent activation of intracellular pathway phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mTOR.[6,7] By selectively blocking signal transduction, mTOR inhibitors can restore the sensitivity to hormonal therapy promoting the effectiveness of exemestane. Pulmonary side effects of selective inhibitors of mTOR (including everolimus)[9,10] represent a class effect, that is common effects of all rapamycin derivatives. They were mainly studied by conventional imaging (radiography and computerized tomography [CT])[12,13] but not yet PROTAC BET degrader-2 evaluated by positron emission tomography with 18F-fluoro-deoxy-glucose combined with computerized tomography (18F-FDG PET/CT). 18F-FDG PET/CT acquired a central role in oncology particularly in breast cancer (initial staging, detection of PROTAC BET degrader-2 recurrence, and evaluation of therapy response in case of metastatic disease). 18F-FDG PET/CT can also diagnose many inflammatory or infectious diseases. Nowadays, no study evaluated lung toxicity of mTOR inhibitors with 18F-FDG PET/CT. The objective of the study was to determine the frequency of everolimus lung side effects in breast cancer and investigate their imaging characteristics in 18F-FDG PET/CT. 2.?Materials and methods 2.1. Patient eligibility Our single-center retrospective descriptive study included patients with metastatic breast cancer initially PROTAC BET degrader-2 treated by association of everolimus (10?mg/d) and exemestane (25?mg/d), similar to the dosage used in clinical practice, from 2012 to 2016, and referred for at least one 18F-FDG PET/CT in our center. Rabbit Polyclonal to CAMK2D All patients performed regular follow-up, consisting in a consultation for early toxicity detection 1 month after treatment initiation, then a quarterly clinical evaluation to assess the effectiveness and tolerance of the treatment, including a 18F-FDG PET/CT and blood biomarker dosage. The management of adverse events depended on the severity: grade I (asymptomatic, radiographic findings only): close monitoring; grade II (symptomatic but not interfering with activities of daily life): dosage adaptation (7.5?mg/d or 5?mg/d); grade III (symptomatic, interfering with activities of daily life, oxygen indicated); or grade IV (life-threatening, ventilatory support indicated): pause then half dose after PROTAC BET degrader-2 resolution of the symptoms. 2.2. 18F-FDG PET/CT Checking of fasting for at least 4?hours and capillary blood glucose before injection. Image acquisition approximately 60 minutes after radiotracer injection. The injected activity and image acquisition protocol varied with PET/CT camera used: Discovery 710 (General Electric, Milwaukee, WI): intravenous injection of 3 MBq/kg (0.08 mCi/kg) of 18F-FDG, then no contrast enhanced CT acquisition (native collimation 16 1.25?mm, auto mA mode with ASIR) and PET acquisition (midthigh-skull base) with 3-dimensional (3D) time of flight mode: 6.