GPER-Targeted, 99mTc-Labeled, Nonsteroidal Ligands Demonstrate Selective Tumor Imaging and In Vivo Estrogen Binding

SummaryFever of unknown origin (FUO) in immunocompetent and non neutropenic patients is defined as recurrent fever of 38,3° C or greater, lasting 2-3 weeks or longer, and undiagnosed after 1 week of appropriate evaluation. The underlying diseases of FUO are numerous and infection accounts for only 20-40% of them. The majority of FUO-patients have autoimmunity and collagen vascular disease and neoplasm, which are responsible for about 50-60% of all cases. In this respect FOU in its classical definition is clearly separated from postoperative and neutropenic fever where inflammation and infection are more common. Although methods that use in-vitro or in-vivo labeled white blood cells (WBCs) have a high diagnostic accuracy in the detection and exclusion of granulocytic pathology, they are only of limited value in FUO-patients in establishing the final diagnosis due to the low prevalence of purulent processes in this collective. WBCs are more suited in evaluation of the focus in occult sepsis. Ga-67 citrate is the only commercially available gamma emitter which images acute, chronic, granulomatous and autoimmune inflammation and also various malignant diseases. Therefore Ga-67 citrate is currently considered to be the tracer of choice in the diagnostic work-up of FUO. The number of Ga-67-scans contributing to the final diagnosis was found to be higher outside Germany than it has been reported for labeled WBCs. F-l 8-2’-deoxy-2-fluoro-D-glucose (FDG) has been used extensively for tumor imaging with PET. Inflammatory processes accumulate the tracer by similar mechanisms. First results of FDG imaging demonstrated, that FDG may be superior to other nuclear medicine imaging modalities which may be explained by the preferable tracer kinetics of the small F-l 8-FDG molecule and by a better spatial resolution of coincidence imaging in comparison to a conventional gamma camera.

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Click Chemistry Expedited Radiosynthesis: Sulfur [18F]fluoride Exchange of Aryl Fluorosulfates

10.26434/chemrxiv.10314647.v1 ◽

2019 ◽

Cited By ~ 1

Author(s):

Qinheng Zheng ◽

Hongtao Xu ◽

Hua Wang ◽

Wen-Ge Han Du ◽

Nan Wang ◽

...

Keyword(s):

Click Chemistry ◽

High Performance ◽

Isotopic Exchange ◽

Tumor Imaging ◽

Radiochemical Yield ◽

Exchange Method ◽

Molar Activity ◽

Positron Emission ◽

Sulfur Fluoride

The lack of simple, efficient [18F]fluorination processes and new target-specific organofluorine probes remains the major challenge of fluorine-18-based positron emission tomography (PET). We report here a fast isotopic exchange method for the radiosynthesis of aryl [18F]fluorosulfate based PET agents enabled by the emerging sulfur fluoride exchange (SuFEx) click chemistry. The method has been applied to the fully-automated 18F-radiolabeling of twenty-five structurally diverse aryl fluorosulfates with excellent radiochemical yield (83–100%) and high molar activity (up to 281 GBq µmol–1) at room temperature in 30 seconds. The purification of radiotracers requires no time-consuming high-performance liquid chromatography (HPLC), but rather a simple cartridge filtration. The utility of aryl [18F]fluorosulfate is demonstrated by the in vivo tumor imaging by targeting poly(ADP-ribose) polymerase 1 (PARP1).

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Cyanine Fluorochrome-Labeled Antibodies in Vivo: Assessment of Tumor Imaging Using Cy3, Cy5, Cy5.5, and Cy7

Cancer Detection and Prevention ◽

10.1046/j.1525-1500.1998.0oa25.x ◽

1998 ◽

Vol 22 (3) ◽

pp. 251-257 ◽

Cited By ~ 37

Author(s):

Byron Ballou ◽

Gregory W. Fisher ◽

Jau-Shyong Deng ◽

Thomas R. Hakala ◽

Meera Srivastava ◽

...

Keyword(s):

Tumor Imaging ◽

In Vivo Assessment

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Dual-Stimulus Responsive Near-Infrared Reversible Ratiometric Fluorescent and Photoacoustic Probe for In Vivo Tumor Imaging

Analytical Chemistry ◽

10.1021/acs.analchem.0c04804 ◽

2021 ◽

Author(s):

Xiao Liu ◽

Xiangyang Gong ◽

Jie Yuan ◽

Xiaopeng Fan ◽

Xingxing Zhang ◽

...

Keyword(s):

Near Infrared ◽

Tumor Imaging ◽

Stimulus Responsive

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In Vivo Chemistry for Pretargeted Tumor Imaging in Live Mice

Angewandte Chemie ◽

10.1002/ange.200906294 ◽

2010 ◽

Vol 122 (19) ◽

pp. 3447-3450 ◽

Cited By ~ 80

Author(s):

Raffaella Rossin ◽

Pascal Renart Verkerk ◽

Sandra M. van den Bosch ◽

Roland C. M. Vulders ◽

Iris Verel ◽

...

Keyword(s):

Tumor Imaging

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Indocyanine Green Loaded Reduced Graphene Oxide for In Vivo Photoacoustic/Fluorescence Dual-Modality Tumor Imaging

Nanoscale Research Letters ◽

10.1186/s11671-016-1288-x ◽

2016 ◽

Vol 11 (1) ◽

Cited By ~ 31

Author(s):

Jingqin Chen ◽

Chengbo Liu ◽

Guang Zeng ◽

Yujia You ◽

Huina Wang ◽

...

Keyword(s):

Graphene Oxide ◽

Indocyanine Green ◽

Reduced Graphene Oxide ◽

Tumor Imaging ◽

Dual Modality ◽

Reduced Graphene

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Hypoxia-sensitive bis(2-(2′-benzothienyl)pyridinato-N,C3′)iridium[poly(n-butyl cyanoacrylate]/chitosan nanoparticles and their phosphorescence tumor imaging in vitro and in vivo

Nanoscale ◽

10.1039/c3nr04349e ◽

2013 ◽

Vol 5 (24) ◽

pp. 12633 ◽

Cited By ~ 13

Author(s):

Yun Zeng ◽

Shaojuan Zhang ◽

Menghui Jia ◽

Yang Liu ◽

Jin Shang ◽

...

Keyword(s):

Tumor Imaging ◽

Chitosan Nanoparticles

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[99mTc]Tc-DB15 in GRPR-Targeted Tumor Imaging with SPECT: From Preclinical Evaluation to the First Clinical Outcomes

Cancers ◽

10.3390/cancers13205093 ◽

2021 ◽

Vol 13 (20) ◽

pp. 5093

Author(s):

Berthold A. Nock ◽

Aikaterini Kaloudi ◽

Panagiotis Kanellopoulos ◽

Barbara Janota ◽

Barbara Bromińska ◽

...

Keyword(s):

Tumor Imaging ◽

Pharmacokinetic Profile ◽

Diglycolic Acid ◽

Preclinical Evaluation ◽

Peptide Receptor ◽

Gastrin Releasing Peptide ◽

Specific Uptake ◽

Grpr Antagonist

Diagnostic imaging and radionuclide therapy of prostate (PC) and breast cancer (BC) using radiolabeled gastrin-releasing peptide receptor (GRPR)-antagonists represents a promising approach. We herein propose the GRPR-antagonist based radiotracer [99mTc]Tc-DB15 ([99mTc]Tc-N4-AMA-DGA-DPhe6,Sar11,LeuNHEt13]BBN(6-13); N4: 6-carboxy-1,4,8,11-tetraazaundecane, AMA: aminomethyl-aniline, DGA: diglycolic acid) as a new diagnostic tool for GRPR-positive tumors applying SPECT/CT. The uptake of [99mTc]Tc-DB15 was tested in vitro in mammary (T-47D) and prostate cancer (PC-3) cells and in vivo in T-47D or PC-3 xenograft-bearing mice as well as in BC patients. DB15 showed high GRPR-affinity (IC50 = 0.37 ± 0.03 nM) and [99mTc]Tc-DB15 strongly bound to the cell-membrane of T-47D and PC-3 cells, according to a radiolabeled antagonist profile. In mice, the radiotracer showed high and prolonged GRPR-specific uptake in PC-3 (e.g., 25.56 ± 2.78 %IA/g vs. 0.72 ± 0.12 %IA/g in block; 4 h pi) and T-47D (e.g., 15.82 ± 3.20 %IA/g vs. 3.82 ± 0.30 %IA/g in block; 4 h pi) tumors, while rapidly clearing from background. In patients with advanced BC, the tracer could reveal several bone and soft tissue metastases on SPECT/CT. The attractive pharmacokinetic profile of [99mTc]DB15 in mice and its capability to target GRPR-positive BC lesions in patients highlight its prospects for a broader clinical use, an option currently being explored by ongoing clinical studies.

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Evaluation of 3-l- and 3-d-[18F]Fluorophenylalanines as PET Tracers for Tumor Imaging

Cancers ◽

10.3390/cancers13236030 ◽

2021 ◽

Vol 13 (23) ◽

pp. 6030

Author(s):

Felicia Krämer ◽

Benedikt Gröner ◽

Chris Hoffmann ◽

Austin Craig ◽

Melanie Brugger ◽

...

Keyword(s):

Amino Acid ◽

Tumor Imaging ◽

Human Tumor ◽

Transport Systems ◽

Acid Decarboxylase ◽

Tumor Xenografts ◽

Tumor Delineation ◽

Mcf 7

Purpose: The preclinical evaluation of 3-l- and 3-d-[18F]FPhe in comparison to [18F]FET, an established tracer for tumor imaging. Methods: In vitro studies were conducted with MCF-7, PC-3, and U87 MG human tumor cell lines. In vivo µPET studies were conducted in healthy rats with/without the inhibition of peripheral aromatic l-amino acid decarboxylase by benserazide pretreatment (n = 3 each), in mice bearing subcutaneous MCF-7 or PC-3 tumor xenografts (n = 10), and in rats bearing orthotopic U87 MG tumor xenografts (n = 14). Tracer accumulation was quantified by SUVmax, SUVmean and tumor-to-brain ratios (TBrR). Results: The uptake of 3-l-[18F]FPhe in MCF-7 and PC-3 cells was significantly higher relative to [18F]FET. The uptake of all three tracers was significantly reduced by the suppression of amino acid transport systems L or ASC. 3-l-[18F]FPhe but not 3-d-[18F]FPhe exhibited protein incorporation. In benserazide-treated healthy rats, brain uptake after 42–120 min was significantly higher for 3-d-[18F]FPhe vs. 3-l-[18F]FPhe. [18F]FET showed significantly higher uptake into subcutaneous MCF-7 tumors (52–60 min p.i.), while early uptake into orthotopic U87 MG tumors was significantly higher for 3-l-[18F]FPhe (SUVmax: 3-l-[18F]FPhe, 107.6 ± 11.3; 3-d-[18F]FPhe, 86.0 ± 4.3; [18F]FET, 90.2 ± 7.7). Increased tumoral expression of LAT1 and ASCT2 was confirmed immunohistologically. Conclusion: Both novel tracers enable accurate tumor delineation with an imaging quality comparable to [18F]FET.

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Recent Experiences and Advances in Contrast-Enhanced Subharmonic Ultrasound

BioMed Research International ◽

10.1155/2015/640397 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 9

Author(s):

John R. Eisenbrey ◽

Anush Sridharan ◽

Ji-Bin Liu ◽

Flemming Forsberg

Keyword(s):

Contrast Agents ◽

Tumor Imaging ◽

Three Dimensional ◽

Ultrasound Contrast Agents ◽

Surrounding Tissue ◽

Contrast Enhanced Ultrasound ◽

Ultrasound Contrast ◽

Contrast Enhanced ◽

Subharmonic Response

Nonlinear contrast-enhanced ultrasound imaging schemes strive to suppress tissue signals in order to better visualize nonlinear signals from blood-pooling ultrasound contrast agents. Because tissue does not generate a subharmonic response (i.e., signal at half the transmit frequency), subharmonic imaging has been proposed as a method for isolating ultrasound microbubble signals while suppressing surrounding tissue signals. In this paper, we summarize recent advances in the use of subharmonic imagingin vivo. These advances include the implementation of subharmonic imaging on linear and curvilinear arrays, intravascular probes, and three-dimensional probes for breast, renal, liver, plaque, and tumor imaging.

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