First-in-human immunoPET imaging of COVID-19 convalescent patients using dynamic total-body PET and a CD8-targeted minibody.

With most of the T cells residing in the tissue, not the blood, developing noninvasive methods for in vivo quantification of their biodistribution and kinetics is important for studying their role in immune response and memory. This study presents the first use of dynamic positron emission tomography (PET) and kinetic modeling for in vivo measurement of CD8+ T cell biodistribution in humans. A 89Zr-labeled CD8-targeted minibody (89Zr-Df-Crefmirlimab) was used with total-body PET in healthy individuals (N = 3) and coronavirus disease 2019 (COVID-19) convalescent patients (N = 5). Kinetic modeling results aligned with T cell-trafficking effects expected in lymphoid organs. Tissue-to-blood ratios from the first 7 hours of imaging were higher in bone marrow of COVID-19 convalescent patients compared to controls, with an increasing trend between 2 and 6 months after infection, consistent with modeled net influx rates and peripheral blood flow cytometry analysis. These results provide a promising platform for using dynamic PET to study the total-body immune response and memory.

First-in-human immunoPET imaging of COVID-19 convalescent patients using dynamic total-body PET and a CD8-targeted minibody.

With the majority of CD8+ T cells residing and functioning in tissue, not blood, developing noninvasive methods for in vivo quantification of their biodistribution and kinetics in humans offers the means for studying their key role in adaptive immune response and memory. This study is the first report on using positron emission tomography (PET) dynamic imaging and compartmental kinetic modeling for in vivo measurement of whole-body biodistribution of CD8+ T cells in human subjects. For this, a 89Zr-labeled minibody with high affinity for human CD8 (89Zr-Df-Crefmirlimab) was used with total-body PET in healthy subjects (N=3) and in COVID-19 convalescent patients (N=5). The high detection sensitivity, total-body coverage, and the use of dynamic scans enabled the study of kinetics simultaneously in spleen, bone marrow, liver, lungs, thymus, lymph nodes, and tonsils, at reduced radiation doses compared to prior studies. Analysis and modeling of the kinetics was consistent with T cell trafficking effects expected from immunobiology of lymphoid organs, suggesting early uptake in spleen and bone marrow followed by redistribution and delayed increasing uptake in lymph nodes, tonsils, and thymus. Tissue-to-blood ratios from the first 7 h of CD8-targeted imaging showed significantly higher values in the bone marrow of COVID-19 patients compared to controls, with an increasing trend between 2 and 6 months post-infection, consistent with net influx rates obtained by kinetic modeling and flow cytometry analysis of peripheral blood samples. These results provide the platform for using dynamic PET scans and kinetic modelling to study total-body immunological response and memory.

Tubal transport of spermatozoa does not appear to be dependent on normal cilia function.

OBJECTIVE: To report the case of a woman with Kartagener's syndrome with complete immotility of ciliae and normal transport of spermatozoa. DESIGN: Case report. PATIENTS: A 31-year-old woman with Kartagener's syndrome. SETTING: Medical university-affiliated teaching hospital. INTERVENTION(S): Ultrasonography, hysterosalpingoscintigraphy using technetium-99m-labeled macroaggregates of human serum albumin, application of oxytocin. MAIN OUTCOME MEASURE(S): Dynamic anteroposterior scintigraphy using a gamma camera. RESULT(S): The transport of labeled macrospheres through the fallopian tube into the peritoneal cavity on the side of the leading follicle, compared to the contralateral oviduct where the labeled material may have accumulated within the fallopian tube, is similar to those reported in normal fertile women. CONCLUSION(S): Transport of spermatozoa is not dependent on normal ciliary function.

Comparison of deformation imaging and velocity imaging for detecting regional inducible ischaemia during dobutamine stress echocardiography.

AIMS: To determine whether Doppler based myocardial tissue velocity imaging (TVI) or strain rate imaging (SRI) is more accurate in detecting stress-induced ischaemia during dobutamine stress echocardiography (DSE). METHODS AND RESULTS: Regional myocardial velocity, displacement, strain rate and strain patterns during DSE were investigated in 44 routine patients with known or suspected coronary artery disease. Simultaneous perfusion scintigraphy defined regional ischaemia. Curves and curved-M-mode patterns were analysed and receiver-operating-characteristics of TVI and SRI parameters were compared by their area under the curve (AUC) in the receiver-operating-characteristics. In non-ischaemic segments, peak systolic velocity and strain rate increased significantly. Unlike SRI, TVI parameters had higher values in basal than in apical segments. In 47 segments of 19 segments DSE-induced ischaemia, which was proven by scintigraphy. In ischaemia, velocity and strain rate increased less. Post-systolic shortening (PSS) was always seen in SRI but not regularly in TVI. Peak systolic velocity and systolic displacement were the best TVI-parameters of stress-induced ischaemia (AUC 0.68 and 0.77, respectively.), in SRI it was the ratio of PSS and maximal segmental deformation (AUC=0.95, p < 0.0001). CONCLUSION: Compared to TVI, SRI parameters showed no major apico-basal gradient and had significantly higher diagnostic accuracy, comparable to conventional reading. SRI thus appears superior to TVI for regional ischaemia detection during DSE and may be preferred to support conventional DSE reading.

Strain-rate imaging during dobutamine stress echocardiography provides objective evidence of inducible ischemia.

BACKGROUND: Interpretation of dobutamine stress echocardiography (DSE) is subjective and strongly dependent on the skills of the reader. Strain-rate imaging (SRI) by tissue Doppler may objectively analyze regional myocardial function. This study investigated SRI markers of stress-induced ischemia and analyzed their applicability in a clinical setting. METHODS AND RESULTS: DSE was performed in 44 patients with known or suspected coronary artery disease. Simultaneous perfusion scintigraphy served as a "gold standard" to define regional ischemia. All patients underwent coronary angiography. Segmental strain and strain rate were analyzed at all stress levels by measuring amplitude and timing of deformation and visual curved M-mode analysis. Results were compared with conventional stress echo reading. In nonischemic segments, peak systolic strain rate increased significantly with dobutamine stress (-1.6+/-0.6 s-1 versus -3.4+/-1.4 s-1, P<0.01), whereas strain during ejection time changed only minimally (-17+/-6% versus -16+/-9%, P<0.05). During DSE, 47 myocardial segments in 19 patients developed scintigraphy-proven ischemia. Strain-rate increase (-1.6+/-0.8 s-1 versus -2.0+/-1.1 s-1, P<0.05) and strain (-16+/-7% versus -10+/-8%, P<0.05) were significantly reduced (both P<0.01 compared with nonischemic). Postsystolic shortening (PSS) was found in all ischemic segments. The ratio of PSS to maximal segmental deformation was the best quantitative parameter to identify stress-induced ischemia. Compared with conventional readings, SRI curved M-mode assessment improved sensitivity/specificity from 81%/82% to 86%/90%. CONCLUSIONS: During DSE, SRI quantitatively and qualitatively differentiates ischemic and nonischemic regional myocardial response to dobutamine stress. The ratio of PSS to maximal strain may be used as an objective marker of ischemia during DSE.

Uptake of [18F]fluorodeoxyglucose in human monocyte-macrophages in vitro.

The fact that fluorine-18 fluorodeoxyglucose ([(18)F]FDG) accumulates in inflammatory lesions as well as in tumours reduces the diagnostic specificity of positron emission tomography (PET) in oncology. The aim of this study was to characterise the uptake of [(18)F]FDG in isolated human monocyte-macrophages (HMMs) in vitro in comparison with that in human glioblastoma (GLI) and pancreatic carcinoma cells (PAN). The purity of HMM preparations was determined by immunohistochemical staining and their functional integrity was assessed by long-term incubation with iodine-131 acetylated bovine serum albumin. [(18)F]FDG uptake in HMMs was quantified as percent of whole [(18)F]FDG activity per well (% ID) or as % ID in relation to total protein mass. [(18)F]FDG uptake in HMMs significantly increased with culture duration, yielding 7.5%+/-0.9% (% ID/100 micro g) at day 14. Stimulation by lipopolysaccharide further enhanced [(18)F]FDG uptake in HMMs by a factor of 2. [(18)F]FDG uptake significantly decreased with increasing glucose concentration in the medium. Radio-thin layer chromatography of intracellular metabolites revealed that [(18)F]FDG was trapped by HMMs mainly as [(18)F]FDG-6-phosphate and [(18)F]FDG-1,6-diphosphate. [(18)F]FDG uptake was in the range of uptake values measured in GLI and PAN. By accumulating [(18)F]FDG in a manner analogous to uptake by tumour cells, activated HMMs may contribute to the [(18)F]FDG uptake values measured by PET in neoplasms.