scholarly journals Chelation with a twist: a bifunctional chelator to enable room temperature radiolabeling and targeted PET imaging with scandium-44

2020 ◽  
Vol 11 (2) ◽  
pp. 333-342 ◽  
Author(s):  
Brett A. Vaughn ◽  
Shin Hye Ahn ◽  
Eduardo Aluicio-Sarduy ◽  
Justin Devaraj ◽  
Aeli P. Olson ◽  
...  

The small-cavity, bifunctional chelator picaga coordinates Sc-44 at room temperature and enables PET imaging of an in vivo tumor target.

2020 ◽  
Vol 117 (49) ◽  
pp. 30928-30933
Author(s):  
Hong-Jun Cho ◽  
Truc T. Huynh ◽  
Buck E. Rogers ◽  
Liviu M. Mirica

Herein, we report a64Cu positron emission tomography (PET) imaging agent that shows appreciable in vivo brain uptake and exhibits high specific affinity for beta-amyloid (Aβ) aggregates, leading to the successful PET imaging of amyloid plaques in the brains of 5xFAD mice versus those of wild-type mice. The employed approach uses a bifunctional chelator with two Aβ-interacting fragments that dramatically improves the Aβ-binding affinity and lipophilicity for favorable blood–brain barrier penetration, while the use of optimized-length spacers between the Cu-chelating group and the Aβ-interacting fragments further improves the in vivo Aβ-binding specificity and brain uptake of the corresponding64Cu PET imaging agent.


2020 ◽  
Author(s):  
Hong-Jun Cho ◽  
Truc T. Huynh ◽  
Buck E. Rogers ◽  
Liviu M. Mirica

Herein, we report to the best of our knowledge the first <sup>64</sup>Cu PET imaging agent that shows appreciable <i>in vivo</i> brain uptake and exhibits high specific affinity for beta-amyloid (Aβ) aggregates, leading to the successful PET imaging of amyloid plaques in the brains of 5xFAD mice versus those of WT mice. The employed approach uses a bifunctional chelator with two Aβ-interacting fragments that dramatically improves the Aβ-binding affinity and lipophilicity for favorable BBB penetration, while the use of optimized-length spacers between the Cu-chelating group and the Aβ-interacting fragments further improves the <i>in vivo</i> Aβ-binding specificity and brain uptake of the corresponding <sup>64</sup>Cu PET imaging agent.


2020 ◽  
Author(s):  
Hong-Jun Cho ◽  
Truc T. Huynh ◽  
Buck E. Rogers ◽  
Liviu M. Mirica

Herein, we report to the best of our knowledge the first <sup>64</sup>Cu PET imaging agent that shows appreciable <i>in vivo</i> brain uptake and exhibits high specific affinity for beta-amyloid (Aβ) aggregates, leading to the successful PET imaging of amyloid plaques in the brains of 5xFAD mice versus those of WT mice. The employed approach uses a bifunctional chelator with two Aβ-interacting fragments that dramatically improves the Aβ-binding affinity and lipophilicity for favorable BBB penetration, while the use of optimized-length spacers between the Cu-chelating group and the Aβ-interacting fragments further improves the <i>in vivo</i> Aβ-binding specificity and brain uptake of the corresponding <sup>64</sup>Cu PET imaging agent.


1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.


2008 ◽  
Vol 1 (2) ◽  
pp. 110-114 ◽  
Author(s):  
A. Gee ◽  
L. Martarello ◽  
J. Passchier ◽  
M. Wishart ◽  
C. Parker ◽  
...  
Keyword(s):  

2021 ◽  
Author(s):  
Cinzia Marceddu ◽  
Adam Hartley ◽  
Mikhail Caga-Anan ◽  
Samata Pandey ◽  
Yasmin Morris ◽  
...  

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.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naomi S. Sta Maria ◽  
Leslie A. Khawli ◽  
Vyshnavi Pachipulusu ◽  
Sharon W. Lin ◽  
Long Zheng ◽  
...  

AbstractQuantitative in vivo monitoring of cell biodistribution offers assessment of treatment efficacy in real-time and can provide guidance for further optimization of chimeric antigen receptor (CAR) modified cell therapy. We evaluated the utility of a non-invasive, serial 89Zr-oxine PET imaging to assess optimal dosing for huLym-1-A-BB3z-CAR T-cell directed to Lym-1-positive Raji lymphoma xenograft in NOD Scid-IL2Rgammanull (NSG) mice. In vitro experiments showed no detrimental effects in cell health and function following 89Zr-oxine labeling. In vivo experiments employed simultaneous PET/MRI of Raji-bearing NSG mice on day 0 (3 h), 1, 2, and 5 after intravenous administration of low (1.87 ± 0.04 × 106 cells), middle (7.14 ± 0.45 × 106 cells), or high (16.83 ± 0.41 × 106 cells) cell dose. Biodistribution (%ID/g) in regions of interests defined over T1-weighted MRI, such as blood, bone, brain, liver, lungs, spleen, and tumor, were analyzed from PET images. Escalating doses of CAR T-cells resulted in dose-dependent %ID/g biodistributions in all regions. Middle and High dose groups showed significantly higher tumor %ID/g compared to Low dose group on day 2. Tumor-to-blood ratios showed the enhanced extravascular tumor uptake by day 2 in the Low dose group, while the Middle dose showed significant tumor accumulation starting on day 1 up to day 5. From these data obtained over time, it is apparent that intravenously administered CAR T-cells become trapped in the lung for 3–5 h and then migrate to the liver and spleen for up to 2–3 days. This surprising biodistribution data may be responsible for the inactivation of these cells before targeting solid tumors. Ex vivo biodistributions confirmed in vivo PET-derived biodistributions. According to these studies, we conclude that in vivo serial PET imaging with 89Zr-oxine labeled CAR T-cells provides real-time monitoring of biodistributions crucial for interpreting efficacy and guiding treatment in patient care.


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