[18F]FPRGD2 PET/CT imaging of integrin αvβ3 levels in patients with locally advanced rectal carcinoma
WITHOFS, Nadia ; Martinive, Philippe ; VANDERICK, Jean et al
in European journal of nuclear medicine and molecular imaging (2016)
PURPOSE: Our primary objective was to determine if [18F]FPRGD2 PET/CT performed at baseline and/or after chemoradiotherapy (CRT) could predict tumour regression grade (TRG) in locally advanced rectal ... [more ▼]
PURPOSE: Our primary objective was to determine if [18F]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 [18F]FPRGD2 and [18F]FDG uptake, to evaluate the correlation between posttreatment [18F]FPRGD2 uptake and tumour microvessel density (MVD) and to determine if [18F]FPRGD2 and FDG PET/CT could predict disease-free survival. METHODS: Baseline [18F]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 [18F]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 [18F]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 [18F]FPRGD2 and FDG SUVmax (Pearson's r = 0.49, p = 0.0026). There was a moderate negative correlation between baseline [18F]FPRGD2 SUVmax and the TRG (Spearman's r = -0.37, p = 0.037), and a [18F]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 [18F]FPRGD2 PET/CT scan the response index, calculated as [(SUVmax1 - SUVmax2)/SUVmax1] x 100 %, was not associated with TRG. Post-treatment [18F]FPRGD2 uptake was not correlated with tumour MVD. Neither [18F]FPRGD2 nor FDG uptake predicted disease-free survival. CONCLUSION: Baseline [18F]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. [less ▲]Detailed reference viewed: 48 (12 ULg)
18F-FPRGD2 PET/CT imaging of integrin αvβ3 in renal carcinomas: Correlation with histopathology
WITHOFS, Nadia ; ; SOMJA, Joan et al
in Journal of Nuclear Medicine (The) (2015)Detailed reference viewed: 58 (16 ULg)
(18)F-FPRGD2 PET/CT imaging of musculoskeletal disorders.
WITHOFS, Nadia ; CHARLIER, Edith ; et al
in Annals of nuclear medicine (2015), 29(10), 839-47
OBJECTIVE: This work reports on musculoskeletal uptake of (18)F-FPRGD2, targeting the integrin alphavbeta3, in patients who had undergone (18)F-FPRGD2 positron emission tomography combined with computed ... [more ▼]
OBJECTIVE: This work reports on musculoskeletal uptake of (18)F-FPRGD2, targeting the integrin alphavbeta3, in patients who had undergone (18)F-FPRGD2 positron emission tomography combined with computed tomography (PET/CT) for oncologic purposes. METHODS: Whole-body (18)F-FPRGD2 PET/CT images of 62 cancer patients were retrospectively reviewed to detect foci of musculoskeletal (18)F-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 (18)F-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 (18)F-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 (18)F-FPRGD2 and FDG was similar with both radiopharmaceuticals, but the target-to-background (blood pool or muscle) ratios were significantly higher with (18)F-FPRGD2 than with FDG (p < 0.0001). CONCLUSION: The (18)F-FPRGD2 uptake in joints, spine degenerative diseases and tendons was highly prevalent in our population. Up to one-third of (18)F-FPRGD2 foci showed no FDG uptake suggesting that (18)F-FPRGD2 signal may not be related to inflammatory angiogenesis only. [less ▲]Detailed reference viewed: 32 (8 ULg)
Twist1 suppresses senescence programs and thereby accelerates and maintains mutant Kras-induced lung tumorigenesis.
; ; et al
in PLoS genetics (2012), 8(5), 1002650
KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents. To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that ... [more ▼]
KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents. To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that other approaches are required. We demonstrate in both a novel transgenic mutant Kras lung cancer mouse model and in human lung tumors that the inhibition of Twist1 restores a senescence program inducing the loss of a neoplastic phenotype. The Twist1 gene encodes for a transcription factor that is essential during embryogenesis. Twist1 has been suggested to play an important role during tumor progression. However, there is no in vivo evidence that Twist1 plays a role in autochthonous tumorigenesis. Through two novel transgenic mouse models, we show that Twist1 cooperates with Kras(G12D) to markedly accelerate lung tumorigenesis by abrogating cellular senescence programs and promoting the progression from benign adenomas to adenocarcinomas. Moreover, the suppression of Twist1 to physiological levels is sufficient to cause Kras mutant lung tumors to undergo senescence and lose their neoplastic features. Finally, we analyzed more than 500 human tumors to demonstrate that TWIST1 is frequently overexpressed in primary human lung tumors. The suppression of TWIST1 in human lung cancer cells also induced cellular senescence. Hence, TWIST1 is a critical regulator of cellular senescence programs, and the suppression of TWIST1 in human tumors may be an effective example of pro-senescence therapy. [less ▲]Detailed reference viewed: 17 (4 ULg)
PET imaging of tumor neovascularization in a transgenic mouse model with a novel 64Cu-DOTA-knottin peptide.
; ; WITHOFS, Nadia et al
in Cancer Research (2010), 70(22), 9022-30
Due to the high mortality of lung cancer, there is a critical need to develop diagnostic procedures enabling early detection of the disease while at a curable stage. Targeted molecular imaging builds on ... [more ▼]
Due to the high mortality of lung cancer, there is a critical need to develop diagnostic procedures enabling early detection of the disease while at a curable stage. Targeted molecular imaging builds on the positive attributes of positron emission tomography/computed tomography (PET/CT) to allow for a noninvasive detection and characterization of smaller lung nodules, thus increasing the chances of positive treatment outcome. In this study, we investigate the ability to characterize lung tumors that spontaneously arise in a transgenic mouse model. The tumors are first identified with small animal CT followed by characterization with the use of small animal PET with a novel 64Cu-1,4,7,10-tetra-azacylododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-knottin peptide that targets integrins upregulated during angiogenesis on the tumor associated neovasculature. The imaging results obtained with the knottin peptide are compared with standard 18F-fluorodeoxyglucose (FDG) PET small animal imaging. Lung nodules as small as 3 mm in diameter were successfully identified in the transgenic mice by small animal CT, and both 64Cu-DOTA-knottin 2.5F and FDG were able to differentiate lung nodules from the surrounding tissues. Uptake and retention of the 64Cu-DOTA-knottin 2.5F tracer in the lung tumors combined with a low background in the thorax resulted in a statistically higher tumor to background (normal lung) ratio compared with FDG (6.01+/-0.61 versus 4.36+/-0.68; P<0.05). Ex vivo biodistribution showed 64Cu-DOTA-knottin 2.5F to have a fast renal clearance combined with low nonspecific accumulation in the thorax. Collectively, these results show 64Cu-DOTA-knottin 2.5F to be a promising candidate for clinical translation for earlier detection and improved characterization of lung cancer. [less ▲]Detailed reference viewed: 35 (3 ULg)