scholarly journals Biodistribution PET/CT Study of Hemoglobin-DFO-89Zr Complex in Healthy and Lung Tumor-Bearing Mice

2020 ◽  
Vol 21 (14) ◽  
pp. 4991
Author(s):  
Łukasz Kiraga ◽  
Gabriele Cerutti ◽  
Agata Braniewska ◽  
Damian Strzemecki ◽  
Zuzanna Sas ◽  
...  

Proteins, as a major component of organisms, are considered the preferred biomaterials for drug delivery vehicles. Hemoglobin (Hb) has been recently rediscovered as a potential drug carrier, but its use for biomedical applications still lacks extensive investigation. To further explore the possibility of utilizing Hb as a potential tumor targeting drug carrier, we examined and compared the biodistribution of Hb in healthy and lung tumor-bearing mice, using for the first time 89Zr labelled Hb in a positron emission tomography (PET) measurement. Hb displays a very high conjugation yield in its fast and selective reaction with the maleimide-deferoxamine (DFO) bifunctional chelator. The high-resolution X-ray structure of the Hb-DFO complex demonstrated that cysteine β93 is the sole attachment moiety to the αβ-protomer of Hb. The Hb-DFO complex shows quantitative uptake of 89Zr in solution as determined by radiochromatography. Injection of 0.03 mg of Hb-DFO-89Zr complex in healthy mice indicates very high radioactivity in liver, followed by spleen and lungs, whereas a threefold increased dosage results in intensification of PET signal in kidneys and decreased signal in liver and spleen. No difference in biodistribution pattern is observed between naïve and tumor-bearing mice. Interestingly, the liver Hb uptake did not decrease upon clodronate-mediated macrophage depletion, indicating that other immune cells contribute to Hb clearance. This finding is of particular interest for rapidly developing clinical immunology and projects aiming to target, label or specifically deliver agents to immune cells.

2019 ◽  
Vol 48 (4) ◽  
pp. 030006051987985
Author(s):  
Yanchao Wang ◽  
Jun Han ◽  
Fantao Zhang ◽  
Zhaoyu Wang ◽  
Dahai Zhao ◽  
...  

Objective This study was performed to compare the radiologic characteristics and pathological presentations of primary pulmonary lymphoma (PPL), explore the possible mechanism underlying its development, summarize its radiologic characteristics, and improve the accuracy of its diagnosis. Methods The medical records of 22 patients pathologically diagnosed with PPL were retrospectively analyzed. Results Chest computed tomography (CT) demonstrated single or multiple nodules and masses in the lungs, patchy opacities or consolidation along the bronchovascular bundle, and no significantly enlarged mediastinal or hilar lymph nodes. All 22 cases of PPL were classified as non-Hodgkin’s lymphoma (NHL) by transbronchial biopsy, CT-guided needle biopsy, and postoperative pathology. Most (16 cases) were marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT). Twelve patients had air bronchograms within the lesion, and 13 showed ill-defined lesions with ground-glass brush-like changes. Conclusion PPL is a rare lung tumor, and most are classified as MALT lymphoma, a subtype of NHL. Chest CT can help to diagnose this disease. Positron emission tomography (PET)/CT is of great clinical value for evaluation of the lesion and patient’s general condition. The possibility of PPL should be considered in patients with characteristic CT and PET/CT findings and mild clinical symptoms, and early treatment should be administered.


2020 ◽  
Vol 16 (3) ◽  
pp. 335-343
Author(s):  
Ying-Tzu Yen ◽  
Xinyue Wang ◽  
Huan Zhang ◽  
Chun Wang ◽  
Zitong Lin ◽  
...  

Chemotherapy has been one of the major standard treatments for a variety of cancers. cis-Dichlorodiamminoplatiunum (II) (cisplatin, CDDP), as one of the anticancer agents, demonstrated excellent efficacy against tumor and has been an indispensable component in chemotherapy, chemoradiation, chemo-molecular targeted therapy and chemo-immunotherapy. However, its therapeutic concentration was limited since its inevitable toxicity. Previously, we have constructed CDDPloaded nanoparticles (NPs) with mixture of poly(ethyleneglycol)-polycaprolactone (PEG-PCL) and polycarprolactone (HOPCL) by a facile method. The most optimal proportion of the two copolymers was selected through a series of physical, chemical, cytological and histological evaluations. In the present study, we explored the mechanisms of NPs and observed the in vivo antitumor effect after administrating CDDP-loaded PEG-PCL NPs. Positron emission tomography as well as computed tomography (PET/CT) were adopted for detecting tumoral metabolic activity. Images from fluorescence microscope revealed superior cellular uptake of CDDP-loaded NPs with rhodamine B aggregated intracellularly in cancer cells. Similar apoptotic rates between free CDDP group and CDDP-loaded NPs group was measured by flow cytometry. Tumor volumes and murine weights confirmed the superiority of CDDP-loaded NPs in therapeutic efficacy as compared with free CDDP. Blood tests showed milder side effects in CDDP-loaded nanoparticle group. PET/CT images illustrated less uptake intensity of FDG in mice received CDDP-loaded NPs than free CDDP. Our results suggest that PEG-PCL/PCL NPs could be a promising antitumor drug carrier for CDDP delivery with solid efficacy and minor side effects.


2018 ◽  
Vol 107 (3) ◽  
pp. 228-236 ◽  
Author(s):  
Sophie Moog ◽  
Sébastien Houy ◽  
Elodie Chevalier ◽  
Stéphane Ory ◽  
Georges Weryha ◽  
...  

Background: 18F-FDOPA positron emission tomography/computed tomography (PET/CT) is a sensitive nuclear imaging technology for the diagnosis of pheochromocytomas (PHEO). However, its utility in determining predictive factors for the secretion of catecholamines remains poorly studied. Methods: Thirty-nine histologically confirmed PHEO were included in this retrospective single-center study. Patients underwent 18F-FDOPA PET/CT before surgery, with an evaluation of several uptake parameters (standardized uptake values [SUVmax and SUVmean] and the metabolic burden [MB] calculated as follows: MB = SUVmean × tumor volume) and measurement of plasma and/or urinary metanephrine (MN), normetanephrine (NM), and chromogranin A. Thirty-five patients were screened for germline mutations in the RET, SDHx, and VHL genes. Once resected, primary cultures of 5 PHEO were used for real-time measurement of catecholamine release by carbon fiber amperometry. Results: The MB of the PHEO positively correlated with 24-h urinary excretion of NM (r = 0.64, p < 0.0001), MN (r = 0.49, p = 0.002), combined MN and NM (r = 0.75, p < 0.0001), and eventually plasma free levels of NM (r = 0.55, p = 0.006). In the mutated patients (3 SDHD, 2 SDHB, 3 NF1, 1 VHL, and 3 RET), a similar correlation was observed between MB and 24-h urinary combined MN and NM (r = 0.86, p = 0.0012). For the first time, we demonstrate a positive correlation between the PHEO-to-liver SUVmax ratio and the mean number of secretory granule fusion events of the corresponding PHEO cells revealed by amperometric spikes (p = 0.01). Conclusion: While the 18F-FDOPA PET/CT MB of PHEO strongly correlates with the concentration of MN, amperometric recordings suggest that 18F-FDOPA uptake could be enhanced by overactivity of catecholamine exocytosis.


Author(s):  
Marco F. Taddio ◽  
Claudia A. Castro Jaramillo ◽  
Peter Runge ◽  
Alain Blanc ◽  
Claudia Keller ◽  
...  

Abstract Purpose The co-stimulatory molecules CD80 and CD86 are upregulated on activated antigen-presenting cells (APC). We investigated whether local APC activation, induced by subcutaneous (s.c.) inoculation of lipopolysaccharides (LPS), can be imaged by positron emission tomography (PET) with CD80/CD86-targeting 64Cu-labelled abatacept. Procedures Mice were inoculated s.c. with extracellular-matrix gel containing either LPS or vehicle (PBS). Immune cell populations were analysed by flow cytometry and marker expression by RT-qPCR. 64Cu-NODAGA-abatacept distribution was analysed using PET/CT and ex vivo biodistribution. Results The number of CD80+ and CD86+ immune cells at the LPS inoculation site significantly increased a few days after inoculation. CD68 and CD86 expression were higher at the LPS than the PBS inoculation site, and CD80 was only increased at the LPS inoculation site. CTLA-4 was highest 10 days after LPS inoculation, when CD80/CD86 decreased again. A few days after inoculation, 64Cu-NODAGA-abatacept distribution to the inoculation site was significantly higher for LPS than PBS (4.2-fold). Co-administration of unlabelled abatacept or human immunoglobulin reduced tracer uptake. The latter reduced the number of CD86+ immune cells at the LPS inoculation site. Conclusions CD80 and CD86 are upregulated in an LPS-induced local inflammation, indicating invasion of activated APCs. 64Cu-NODAGA-abatacept PET allowed following APC activation over time.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Yu Guo ◽  
Yuanming Feng ◽  
Jian Sun ◽  
Ning Zhang ◽  
Wang Lin ◽  
...  

The combination of positron emission tomography (PET) and CT images provides complementary functional and anatomical information of human tissues and it has been used for better tumor volume definition of lung cancer. This paper proposed a robust method for automatic lung tumor segmentation on PET/CT images. The new method is based on fuzzy Markov random field (MRF) model. The combination of PET and CT image information is achieved by using a proper joint posterior probability distribution of observed features in the fuzzy MRF model which performs better than the commonly used Gaussian joint distribution. In this study, the PET and CT simulation images of 7 non-small cell lung cancer (NSCLC) patients were used to evaluate the proposed method. Tumor segmentations with the proposed method and manual method by an experienced radiation oncologist on the fused images were performed, respectively. Segmentation results obtained with the two methods were similar and Dice’s similarity coefficient (DSC) was 0.85 ± 0.013. It has been shown that effective and automatic segmentations can be achieved with this method for lung tumors which locate near other organs with similar intensities in PET and CT images, such as when the tumors extend into chest wall or mediastinum.


2007 ◽  
Vol 2007 ◽  
pp. 1-5 ◽  
Author(s):  
Guangming Lu ◽  
Zhongqiu Wang ◽  
Hong Zhu ◽  
Linfeng Chang ◽  
Yingxin Chen ◽  
...  

Purpose.To evaluate the diagnosis value of integrated positron emission tomography and computed tomography (PET/CT) with lung masses, this study emphasized the correlation between tumor size and maximum standardized uptake value (SUVmax) in selected regions of interest (ROI) of lung masses.Material and Methods.A retrospective analysis was performed on 85 patients with solid pulmonary lesions, all verified by pathology. The morphology, edge (speculated margins and lobule), size, density of pulmonary masses, and on-chest CT images were reviewed. The SUVmax in ROI of pulmonary masses was calculated.Results.Among the 85 patients with lung masses, 59 patients presented with pulmonary malignant neoplasm and 26 patients with benign lesions. The sensitivity, specificity, and accuracy were 89.8%, 61.5%, 81.2%, respectively, for PET measurement only, 88.1%, 65.4%, 81.2% for CT only, and 96.6%, 80.8%, 91.8% for PET/CT. The size of pulmonary malignant neoplasm in the 59 patients was apparently correlated with the ROI's SUVmax (r=0.617,P<.001). However, the size of pulmonary benign mass in the 26 patients was not correlated with the SUVmax.Conclusion.PET/CT is of greater value in characterization of lung masses than PET and CT performed separately. The examination of lung tumor can be further specified by the correlation between the size of pulmonary malignant neoplasm and the ROI's SUVmax.


2005 ◽  
Vol 44 (S 01) ◽  
pp. S46-S50 ◽  
Author(s):  
M. Dawood ◽  
N. Lang ◽  
F. Büther ◽  
M. Schäfers ◽  
O. Schober ◽  
...  

Summary:Motion in PET/CT leads to artifacts in the reconstructed PET images due to the different acquisition times of positron emission tomography and computed tomography. The effect of motion on cardiac PET/CT images is evaluated in this study and a novel approach for motion correction based on optical flow methods is outlined. The Lukas-Kanade optical flow algorithm is used to calculate the motion vector field on both simulated phantom data as well as measured human PET data. The motion of the myocardium is corrected by non-linear registration techniques and results are compared to uncorrected images.


2011 ◽  
Vol 14 (5) ◽  
pp. 283 ◽  
Author(s):  
Andre Plass ◽  
Maximilian Y. Emmert ◽  
Oliver Gaemperli ◽  
Hatem Alkadhi ◽  
Philipp Kaufmann ◽  
...  

<p><b>Background:</b> We evaluated how comprehensive assessment of coronary artery lesions and their hemodynamic relevance by means of hybrid positron emission tomography (PET) and computed tomography (CT) imaging would affect decision-making in coronary artery bypass surgery (CABG), compared with using invasive coronary angiography (ICA) alone.</p><p><b>Methods:</b> After undergoing ICA, 27 patients (21 men and 6 women; mean SD age, 66 � 10 years) planned for cardiac surgery were scheduled for myocardial perfusion stress/rest evaluation with [13N]ammonia PET and CT coronary angiography. Only ICA was available to the surgeon. Postoperatively, the performed CABG was compared with the hypothetical strategy based on hybrid PET/CT findings (regional coronary flow reserve [CFR], myocardial perfusion defects). Procedures included CABG (n = 18) alone, CABG combined with valve replacement (n = 6), and CABG combined with isolated valve replacement (n = 3). A total of 56 bypass grafts (28 venous and 28 arterial) and 66 distal anastomoses were placed.</p><p><b>Results:</b> CT evaluation showed 93% concordance (66/71) with ICA regarding significant stenoses, with sensitivity, specificity, positive predictive value, and negative predictive value of 93.1%, 98.7%, 94.4%, and 98.4%, respectively. In the PET scan, 16 patients had 1 ischemic region, and 12 patients had 1 scar region, including 5 patients who presented with mixed conditions (scar and ischemia). One patient had a completely normal myocardium. Compared with the performed surgery, PET/CT fusion evaluation showed that of the performed anastomoses, 48% had documented ischemia (with a CFR <2 in 86%), 38% were nonischemic (although a CFR value <2 was found in 78%), and 14% had scar tissue (fixed perfusion defect).</p><p><b>Conclusions:</b> Although <50% of bypasses were placed to areas with myocardial ischemia, the CFR was low in the majority of nonischemic regions, a finding that may have important prognostic relevance. PET/CT fusion imaging could potentially influence planning for CABG and provide incremental prognostic information.</p>


Sign in / Sign up

Export Citation Format

Share Document