scholarly journals Early Detection of Tumor Response to Chemotherapy by 3′-Deoxy-3′-[18F]Fluorothymidine Positron Emission Tomography: The Effect of Cisplatin on a Fibrosarcoma Tumor Model In vivo

2005 ◽  
Vol 65 (10) ◽  
pp. 4202-4210 ◽  
Author(s):  
Julius Leyton ◽  
John R. Latigo ◽  
Meg Perumal ◽  
Harmandeep Dhaliwal ◽  
Qimin He ◽  
...  
2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Adrienn Kis ◽  
Judit P. Szabó ◽  
Noémi Dénes ◽  
Adrienn Vágner ◽  
Gábor Nagy ◽  
...  

Introduction. Hypoxia-induced ανβ3 integrin and aminopeptidase N (APN/CD13) receptor expression play an important role in tumor neoangiogenesis. APN/CD13-specific 68Ga-NOTA-c(NGR), ανβ3 integrin-specific 68Ga-NODAGA-[c(RGD)]2, and hypoxia-specific 68Ga-DOTA-nitroimidazole enable the in vivo detection of the neoangiogenic process and the hypoxic regions in the tumor mass using positron emission tomography (PET) imaging. The aim of this study was to evaluate whether 68Ga-NOTA-c(NGR) and 68Ga-DOTA-nitroimidazole allow the in vivo noninvasive detection of the temporal changes of APN/CD13 expression and hypoxia in experimental He/De tumors using positron emission tomography. Materials and Methods. 5×106 hepatocellular carcinoma (He/De) cells were used for the induction of a subcutaneous tumor model in Fischer-344 rats. He/De tumor-bearing animals were anaesthetized, and 90 min after intravenous injection of 10.2±1.1 MBq 68Ga-NOTA-c(NGR) or 68Ga-NODAGA-[c(RGD)]2 (as angiogenesis tracers) or 68Ga-DOTA-nitroimidazole (for hypoxia imaging), whole-body PET/MRI scans were performed. Results. Hypoxic regions and angiogenic markers (αvβ3 integrin and APN/CD13) were determined using 68Ga-NOTA-c(NGR), 68Ga-DOTA-nitroimidazole, and 68Ga-NODAGA-[c(RGD)]2 in subcutaneously growing He/De tumors in rats. 68Ga-NOTA-c(NGR) showed the strong APN/CD13 positivity of He/De tumors in vivo, by which observation was confirmed by western blot analysis. By the qualitative analysis of PET images, heterogenous accumulation was found inside He/De tumors using all radiotracers. Significantly (p≤0.01) higher SUVmean and SUVmax values were found in the radiotracer avid regions of the tumors than those of the nonavid areas using hypoxia and angiogenesis-specific radiopharmaceuticals. Furthermore, a strong correlation was found between the presence of angiogenic markers, the appearance of hypoxic regions, and the tumor volume using noninvasive in vivo PET imaging. Conclusion. 68Ga-DOTA-nitroimidazole and 68Ga-NOTA-c(NGR) are suitable diagnostic radiotracers for the detection of the temporal changes of hypoxic areas and neoangiogenic molecule (CD13) expression, which vary during tumor growth in a hepatocellular carcinoma model.


2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Carlos Velasco ◽  
Adriana Mota-Cobián ◽  
Jesús Mateo ◽  
Samuel España

Abstract Background Multi-tracer positron emission tomography (PET) imaging can be accomplished by applying multi-tracer compartment modeling. Recently, a method has been proposed in which the arterial input functions (AIFs) of the multi-tracer PET scan are explicitly derived. For that purpose, a gamma spectroscopic analysis is performed on blood samples manually withdrawn from the patient when at least one of the co-injected tracers is based on a non-pure positron emitter. Alternatively, these blood samples required for the spectroscopic analysis may be obtained and analyzed on site by an automated detection device, thus minimizing analysis time and radiation exposure of the operating personnel. In this work, a new automated blood sample detector based on silicon photomultipliers (SiPMs) for single- and multi-tracer PET imaging is presented, characterized, and tested in vitro and in vivo. Results The detector presented in this work stores and analyzes on-the-fly single and coincidence detected events. A sensitivity of 22.6 cps/(kBq/mL) and 1.7 cps/(kBq/mL) was obtained for single and coincidence events respectively. An energy resolution of 35% full-width-half-maximum (FWHM) at 511 keV and a minimum detectable activity of 0.30 ± 0.08 kBq/mL in single mode were obtained. The in vivo AIFs obtained with the detector show an excellent Pearson’s correlation (r = 0.996, p < 0.0001) with the ones obtained from well counter analysis of discrete blood samples. Moreover, in vitro experiments demonstrate the capability of the detector to apply the gamma spectroscopic analysis on a mixture of 68Ga and 18F and separate the individual signal emitted from each one. Conclusions Characterization and in vivo evaluation under realistic experimental conditions showed that the detector proposed in this work offers excellent sensibility and stability. The device also showed to successfully separate individual signals emitted from a mixture of radioisotopes. Therefore, the blood sample detector presented in this study allows fully automatic AIFs measurements during single- and multi-tracer PET studies.


Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1041
Author(s):  
Jun Nakata ◽  
Kayako Isohashi ◽  
Yoshihiro Oka ◽  
Hiroko Nakajima ◽  
Soyoko Morimoto ◽  
...  

Assessment of tumor response during treatment is one of the most important purposes of imaging. Before the appearance of immunotherapy, response evaluation criteria in solid tumors (RECIST) and positron emission tomography response criteria in solid tumors (PERCIST) were, respectively, the established morphologic and metabolic response criteria, and cessation of treatment was recommended when progressive disease was detected according to these criteria. However, various types of immunotherapy have been developed over the past 20 years, which show novel false positive findings on images, as well as distinct response patterns from conventional therapies. Antitumor immune response itself causes 18F-fluorodeoxyglucose (FDG) uptake in tumor sites, known as “flare phenomenon”, so that positron emission tomography using FDG can no longer accurately identify remaining tumors. Furthermore, tumors often initially increase, followed by stability or decrease resulting from immunotherapy, which is called “pseudoprogression”, so that progressive disease cannot be confirmed by computed tomography or magnetic resonance imaging at a single time point. As a result, neither RECIST nor PERCIST can accurately predict the response to immunotherapy, and therefore several new response criteria fixed for immunotherapy have been proposed. However, these criteria are still controversial, and also require months for response confirmation. The establishment of optimal response criteria and the development of new imaging technologies other than FDG are therefore urgently needed. In this review, we summarize the false positive images and the revision of response criteria for each immunotherapy, in order to avoid discontinuation of a truly effective immunotherapy.


Author(s):  
Rui Luo ◽  
Lei Wang ◽  
Fei Ye ◽  
Yan-Rong Wang ◽  
Wei Fang ◽  
...  

Abstract Background This study aimed to evaluate the biodistribution and kinetics of [18F]FEDAC targeting the translocator protein TSPO in the myocardium, and to explore its use for the identification of mitochondrial dysfunction. We also assessed the feasibility of [18F]FEDAC for the early detection of mitochondrial dysfunction associated with myocardial ischemia (MI). Methods The radiochemical purity and stability of [18F]FEDAC were analyzed by radio-high-performance liquid chromatography (radio-HPLC). Its biodistribution and kinetics were evaluated by dissection and dynamic imaging using micro-positron emission tomography–computed tomography (micro-PET–CT) in healthy mice. [18F]FEDAC was also applied in an MI rat model and in sham-operated controls. Mitochondrial changes were observed by immunohistochemical staining and electron microscopy. Results Radioactivity levels (%ID/g) in the myocardium in normal mice, determined by [18F]FEDAC, were 8.32 ± 0.80 at 5 min and 2.40 ± 0.10 at 60 min. PET showed significantly decreased uptake by injured cardiac tissue in MI rats, with maximal normal-to-ischemic uptake ratios of 10.47 ± 3.03 (1.5 min) and 3.92 ± 1.12 (27.5 min) (P = 0.025). Immunohistochemistry confirmed that TSPO expression was decreased in MI rats. Mitochondrial ultrastructure demonstrated significant swelling and permeability. Conclusion [18F]FEDAC uptake is reduced in the injured myocardium, consistent with mitochondrial dysfunction. These results may provide new evidence to aid the early detection of mitochondrial dysfunction associated with myocardial ischemic injury.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Johannes Notni ◽  
Florian T. Gassert ◽  
Katja Steiger ◽  
Peter Sommer ◽  
Wilko Weichert ◽  
...  

Following publication of the original article [1], the authors have reported an error in the ‘Histopathology’ (under ‘Materials and methods’) section of the article that compromises the reproducibility of the paper.


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