scholarly journals Attempts to Target Staphylococcus aureus Induced Osteomyelitis Bone Lesions in a Juvenile Pig Model by Using Radiotracers

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4329
Author(s):  
Pia Afzelius ◽  
Aage Alstrup ◽  
Ole Nielsen ◽  
Karin Nielsen ◽  
Svend Jensen

Background [18F]FDG Positron Emission Tomography cannot differentiate between sterile inflammation and infection. Therefore, we, aimed to develop more specific radiotracers fitted for differentiation between sterile and septic infection to improve the diagnostic accuracy. Consequently, the clinicians can refine the treatment of, for example, prosthesis-related infection. Methods: We examined different target points; Staphylococcus aureus biofilm (68Ga-labeled DOTA-K-A9 and DOTA-GSGK-A11), bone remodeling ([18F]NaF), bacterial cell membranes ([68Ga]Ga-Ubiquicidin), and leukocyte trafficking ([68Ga]Ga-DOTA-Siglec-9). We compared them to the well-known glucose metabolism marker [18F]FDG, in a well-established juvenile S. aureus induced osteomyelitis (OM) pig model. Results: [18F]FDG accumulated in the OM lesions seven days after bacterial inoculation, but disappointingly we were not able to identify any tracer accumulation in OM with any of the supposedly more specific tracers. Conclusion: These negative results are, however, relevant to report as they may save other research groups from conducting the same animal experiments and provide a platform for developing and evaluating other new potential tracers or protocol instead.

2019 ◽  
Vol 20 (10) ◽  
pp. 2564 ◽  
Author(s):  
Clément Bailly ◽  
Sébastien Gouard ◽  
François Guérard ◽  
Benjamin Chalopin ◽  
Thomas Carlier ◽  
...  

Although positron emission tomography (PET) imaging with 18-Fluorodeoxyglucose (18F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker for the identification of myeloma cells and could be used in phenotype tumor imaging. In this study, we used an anti-CD138 murine antibody (9E7.4) radiolabeled with copper-64 (64Cu) or zirconium-89 (89Zr) and compared them in a syngeneic mouse model to select the optimal tracers for MM PET imaging. Then, 9E7.4 was conjugated to TE2A-benzyl isothiocyanate (TE2A) and desferrioxamine (DFO) chelators for 64Cu and 89Zr labeling, respectively. 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 antibodies were evaluated by PET imaging and biodistribution studies in C57BL/KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions and were compared to 18F-FDG-PET imaging. In biodistribution and PET studies, 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 displayed comparable good tumor uptake of subcutaneous tumors. On the bone lesions, PET imaging with 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 showed higher uptake than with 18F-FDG-PET. Comparison of both 9E7.4 conjugates revealed higher nonspecific bone uptakes of 89Zr-DFO-9E7.4 than 64Cu-TE2A-9E7.4. Because of free 89Zr’s tropism for bone when using 89Zr-anti-CD138, 64Cu-anti-CD138 antibody had the most optimal tumor-to-nontarget tissue ratios for translation into humans as a specific new imaging radiopharmaceutical agent in MM.


2008 ◽  
Vol 47 (01) ◽  
pp. 18-23 ◽  
Author(s):  
M. Wehrschuetz ◽  
B. Bisail ◽  
M. Woltsche ◽  
T. Schwarz ◽  
H. Lanz ◽  
...  

SummaryAim: 67Ga citrate has been used long and successfully to diagnose and stage sarcoidosis. 18F-fluorodeoxyglucose (18F-FDG) has been suggested as a positron emission tomography (PET) tracer for sarcoidosis imaging. This study aimed to analyze possible advantages of 18F-FDG-PET over 67Ga citrate scintigraphy during the primary assessment of patients with sarcoidosis. Patients and methods: Twentyfour patients (11 men, 13 women, aged 52 years ±12.4) with histologically proven sarcoidosis were investigated with 18F-FDG and 67Ga citrate. Equipment included a fullring PET scanner (ECAT EXACT HR+, Siemens/CTI, Knoxville TN, USA) and a double-headed gamma camera (ECAM, Siemens, Illinois, USA) for scintigraphy. The mean time difference between the two studies was 6.5 days (range: 5–8 days). Results: There was a significant difference in the detection of pulmonary and nonpulmonary sarcoidosis lesions between planar 67Ga citrate scans and 18F-FDG-PET images (<0.0021). A total of 64 lesions were detected with 67Ga citrate scans in the thorax and elsewhere with a mean of 2.6 lesions (4%) per patient, while 85 lesions were found with 18F-FDG-PET, with a mean of 3.5 lesions (4.1%) per patient. There was complete agreement between 18F-FDG and 67Ga citrate in thoracic manifestations in four (16.6%) patients, and in non-thoracic manifestations in five (20.8%) patients. The interobserver variability showed a kappa value of 0.79. Conclusion: 67Ga citrate and 18F-FDG are useful tracers for diagnostic evaluation of thoracic sarcoidosis. 18F-FDG seems to be more suitable for imaging the mediastinum, the bi-hilar lymph nodes, the posterior regions of the lungs and non-thoracic lesions. Further prospective studies are needed to clarify the role of both tracers in early diagnosis and staging of sarcoidosis, and to resolve questions concerning medical treatment and follow-up.


Author(s):  
Keisuke Miyake ◽  
Kenta Suzuki ◽  
Tomoya B Ogawa ◽  
Daisuke Ogawa ◽  
Tetsuhiro Hatakeyama ◽  
...  

Abstract Background The molecular diagnosis of gliomas such as isocitrate dehydrogenase (IDH) status (wild-type [wt] or mutation [mut]) is especially important in the 2016 WHO classification. Positron emission tomography (PET) has afforded molecular and metabolic diagnostic imaging. The present study aimed to define the interrelationship between the 2016 WHO classification of gliomas and the integrated data from PET images using multiple tracers, including 18F-fluorodeoxyglucose ( 18F-FDG), 11C-methionine ( 11C-MET), 18F-fluorothymidine ( 18F-FLT), and 18F-fluoromisonidazole ( 18F-FMISO). Methods This retrospective, single-center study comprised 113 patients with newly diagnosed glioma based on the 2016 WHO criteria. Patients were divided into four glioma subtypes (Mut, Codel, Wt, and glioblastoma multiforme [GBM]). Tumor standardized uptake value (SUV) divided by mean normal cortical SUV (tumor-normal tissue ratio [TNR]) was calculated for 18F-FDG, 11C-MET, and 18F-FLT. Tumor-blood SUV ratio (TBR) was calculated for 18F-FMISO. To assess the diagnostic accuracy of PET tracers in distinguishing glioma subtypes, a comparative analysis of TNRs and TBR as well as the metabolic tumor volume (MTV) were calculated by Scheffe’s multiple comparison procedure for each PET tracer following the Kruskal–Wallis test. Results The differences in mean 18F-FLT TNR and 18F-FMISO TBR were significant between GBM and other glioma subtypes (p &lt; 0.001). Regarding the comparison between Gd-T1WI volumes and 18F-FLT MTVs or 18F-FMISO MTVs, we identified significant differences between Wt and Mut or Codel (p &lt; 0.01). Conclusion Combined administration of four PET tracers might aid in the preoperative differential diagnosis of gliomas according to the 2016 WHO criteria.


Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 557
Author(s):  
Kirsten Korsholm ◽  
Michala Reichkendler ◽  
Louise Alslev ◽  
Åse Krogh Rasmussen ◽  
Peter Oturai

Our objective was to evaluate the frequency of malignancy in incidental thyroidal uptake on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in a cohort of Danish patients, and furthermore to evaluate the impact of thyroid scinti-graphy in the diagnostic work-up. All whole-body PET/CT reports from 1 January 2010 to 31 December 2013 were retrospectively reviewed and further analyzed if visually increased thyroidal FDG uptake was reported. Patient electronic files were searched for further thyroid evaluation. Of 13,195 18F-FDG-PET/CT scans in 9114 patients, 312 PET/CT reports mentioned incidental thyroid FDG-uptake, and 279 patients were included in the study (3.1%). The thyroid was further investigated in 137 patients (49%), and 75 patients underwent thyroid scintigraphy. A total of 57 patients had a thyroid biopsy and 21 proceeded to surgery. Surgical specimens displayed malignancy in 10 cases, and one thyroid malignancy was found by autopsy. Hence, 11 patients were diagnosed with thyroid malignancies among 279 patients with incidental thyroid 18F-FDG uptake (3.9%). In 34 patients, a biopsy was avoided due to the results of the thyroid scintigraphy. We conclude that patients with thyroid incidentalomas can benefit from further diagnostic work-up including a thyroid scintigraphy.


Blood ◽  
2003 ◽  
Vol 102 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Karoline Spaepen ◽  
Sigrid Stroobants ◽  
Patrick Dupont ◽  
Peter Vandenberghe ◽  
Johan Maertens ◽  
...  

Abstract The study assessed the prognostic value of fluorine 18-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) after salvage chemotherapy before high-dose chemotherapy with stem cell transplantation (HDT/SCT) in patients with induction failure or relapsing chemosensitive lymphoma. Retrospective analysis of the clinical and conventional imaging data of 60 patients scheduled for HDT/SCT was performed in parallel with the analysis of the [18F]FDG-PET results. To determine the ability of [18F]FDG-PET to predict clinical outcome, PET images were reread without knowledge of conventional imaging and clinical history. Presence or absence of abnormal [18F]FDG uptake was related to progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis. Thirty patients showed a negative [18F]FDG-PET scan before HDT/SCT; 25 of those remained in complete remission, with a median follow-up of 1510 days. Two patients died due to a treatment-related mortality but without evidence of recurrent disease at that time (228-462 days). Only 3 patients had a relapse (median PFS, 1083 days) after a negative [18F]FDG-PET scan. Persistent abnormal [18F]FDG uptake was seen in 30 patients and 26 progressed (median PFS, 402 days); of these 26, 16 died from progressive disease (median OS, 408 days). Four patients are still in complete remission after a positive scan. Comparison between groups indicated a statistically significant association between [18F]FDG-PET findings and PFS (P &lt; .000001) and OS (P &lt; .00002). [18F]FDG-PET has an important prognostic role in the pretransplantation evaluation of patients with lymphoma and enlarges the concept of chemosensitivity used to select patients for HDT/SCT. (Blood. 2003;102:53-59)


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1264
Author(s):  
Jaume Mora ◽  
Alicia Castañeda ◽  
Maria Cecilia Colombo ◽  
Maite Gorostegui ◽  
Fernando Gomez ◽  
...  

Background: Neuroblastic tumors (NBTs) originate from a block in the process of differentiation. Histologically, NBTs are classified in neuroblastoma (NB), ganglioneuroblastoma (GNB), and ganglioneuroma (GN). Current therapy for high-risk (HR) NB includes chemotherapy, surgery, radiotherapy, and anti-GD2 monoclonal antibodies (mAbs). Anti-GD2 mAbs induce immunological cytoxicity but also direct cell death. Methods: We report on patients treated with naxitamab for chemorefractory NB showing lesions with long periods of stable disease. Target lesions with persisting 123I-Metaiodobenzylguanidine (MIBG) uptake after 4 cycles of immunotherapy were further evaluated by functional Magnetic Resonance Imaging (MRI) and/or Fluorodeoxyglucose (FDG)-positron emission tomography (PET). MIBG avid lesions that became non-restrictive on MRI (apparent diffusion coefficient (ADC) > 1) and/or FDG-PET negative (SUV < 2) were biopsied. Results: Twenty-seven relapse/refractory (R/R) HR-NB patients were enrolled on protocol Ymabs 201. Two (7.5%) of the 27 showed persistent bone lesions on MIBG, ADC high, and/or FDG-PET negative. Forty-four R/R HR-NB patients received chemo-immunotherapy. Twelve (27%) of the 44 developed persistent MIBG+ but FDG-PET- and/or high ADC lesions. Twelve (86%) of the 14 cases identified were successfully biopsied producing 16 evaluable samples. Histology showed ganglioneuroma maturing subtype in 6 (37.5%); ganglioneuroma mature subtype with no neuroblastic component in 4 (25%); differentiating NB with no Schwannian stroma in 5 (31%); and undifferentiated NB without Schwannian stroma in one (6%). Overall, 10 (62.5%) of the 16 specimens were histopathologically fully mature NBTs. Conclusions: Our results disclose an undescribed mechanism of action for naxitamab and highlight the limitations of conventional imaging in the evaluation of anti-GD2 immunotherapy clinical efficacy for HR-NB.


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