scholarly journals An activated excretion-retarded tumor imaging strategy towards metabolic organs

2021 ◽  
Author(s):  
Da-Yong Hou ◽  
Man-Di Wang ◽  
Xing-Jie Hu ◽  
Zhi-Jia Wang ◽  
Ni-Yuan Zhang ◽  
...  
Keyword(s):  
Tumor Imaging ◽  
Imaging Strategy

scholarly journals A Pretargeted Imaging Strategy for EGFR Positive Colorectal Carcinoma via the Modulation of Tz-radioligand Pharmacokinetics

2020 ◽  
Author(s):  
Lin Qiu ◽  
Hui Tan ◽  
Qingyu Lin ◽  
Zhan Si ◽  
Jun Zhou ◽  
...  
Keyword(s):  
Tumor Imaging ◽  
Molecular Probes ◽  
Ideal Situation ◽  
Imaging Results ◽  
Imaging Strategy ◽  
Xenograft Mice ◽  
The Stability ◽  
In Vitro Stability

Abstract Objective: Previously, we successfully developed a pretargeted imaging strategy (Atezolizumab-TCO/99mTc-HYNIC-PEG11-Tz), which is a powerful tool for evaluating Programmed Cell Death Ligand-1 (PD-L1) expression in xenograft mice tumor models. However, the surplus unclicked 99mTc-HYNIC-PEG11-Tz is cleared somewhat sluggishly through the intestines. This is certainly not an ideal situation for imaging for colorectal cancer (CRC). In order to shift the excretion of the Tz-radioligand to the renal system, we have sought to develop a novel Tz-radioligand by adding a polypeptide linker between HYNIC and PEG11. Methods: Pretargeted molecular probes 99mTc-HYNIC-Polypeptide-PEG11-Tz and Cetuximab-TCO were synthesized. The stability of 99mTc-HYNIC-Polypeptide-PEG11-Tz was evaluated in vitro, and its blood pharmacokinetic test was performed in vivo. In vitro ligation reactivity of 99mTc-HYNIC-Polypeptide-PEG11-Tz towards Cetuximab-TCO was tested. The biodistribution and imaging of 99mTc-HYNIC-Polypeptide-PEG11-Tz was performed to observe the clear pathway of this novel Tz-radioligand. Pretargeted biodistribution of three different accumulation intervals was performed to determine the optimal pretargeted interval time. Comparison of pretargeted (Cetuximab-TCO 48 h/99mTc-HYNIC-PEG11-Tz 6 h) and (Cetuximab-TCO 48 h/99mTc-HYNIC-Polypeptide-PEG11-Tz 6 h) imagings was performed to show the effect of the two Tz-radioligands with different excretion pathway on tumor imaging. Results: 99mTc-HYNIC-Polypeptide-PEG11-Tz showed favorable in vitro stability and rapid blood clearance in mice. SEC-HPLC revealed almost complete reaction between Cetuximab-TCO and 99mTc-HYNIC-Polypeptide-PEG11-Tz in vitro, with the 8:1 Tz-to-mAb reaction providing a conversion yield of 87.83 ± 3.27%. The biodistribution and imaging of 99mTc-HYNIC-Polypeptide-PEG11-Tz demonstrated that the Tz-radioligand was cleared through kidneys. After allowing 24 h, 48 h and 72 h for accumulation of Cetuximab-TCO in HCT116 tumor, pretargeted biodistribution revealed the tumor-to-blood ratio was 0.83 ± 0.13, 1.40 ± 0.31, and 1.15 ± 0.21, respectively. Both pretargeted (Cetuximab-TCO 48 h/99mTc-HYNIC-PEG11-Tz 6 h) and (Cetuximab-TCO 48 h/99mTc-HYNIC-Polypeptide-PEG11-Tz 6 h) imaging delineated the HCT116 tumor clearly. However, pretargeted imaging strategy using Cetuximab-TCO/99mTc-HYNIC-Polypeptide-PEG11-Tz could be used for diagnosing CRC since the surplus unclicked 99mTc-HYNIC-Polypeptide-PEG11-Tz is cleared through urinary system and produces low abdominal uptake background. Conclusion: We developed a novel pretargeted imaging strategy (Cetuximab-TCO/99mTc-HYNIC-Polypeptide-PEG11-Tz) for imaging CRC since the surplus unclicked 99mTc-HYNIC-Polypeptide-PEG11-Tz produces low abdominal uptake background, which broadens the application scope of pretargeted imaging strategy.

scholarly journals A Pretargeted Imaging Strategy for EGFR Positive Colorectal Carcinoma via the Modulation of Tz-radioligand Pharmacokinetics

2020 ◽  
Author(s):  
Lin Qiu ◽  
Hui Tan ◽  
Qingyu Lin ◽  
Zhan Si ◽  
Jun Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Radiochemical Purity ◽  
Binding Assay ◽  
Tumor Imaging ◽  
Hct116 Cell ◽  
Size Exclusion ◽  
Liquid Chromatograph ◽  
Imaging Results ◽  
Imaging Strategy

Abstract Objective: Previously, we successfully developed a 6-hydrazinonicotinic acid (HYNIC)-modified terazine (Tz) derivative (HYNIC-PEG11-Tz) and labeled with Technetium-99m (99mTc) with a high radiochemical purity. The pretargeted imaging strategy using Atezolizumab-TCO/99mTc-HYNIC-PEG11-Tz is a powerful tool for evaluating Programmed Cell Death Ligand-1 (PD-L1) expression in xenograft mice tumor models. However, the surplus unclicked 99mTc-HYNIC-PEG11-Tz is cleared somewhat sluggishly through the intestines. This is certainly not an ideal situation for imaging for abdominal tumors, especially for colorectal cancer. In order to shift the excretion of the Tz-radioligand to the renal system, we have sought to develop a novel Tz-radioligand by add a polypeptide linker between HYNIC and PEG11. Methods: A polypeptide-modified Tz (HYNIC-Polypeptide-PEG11-Tz) was synthesized and radiolabeled with 99mTc, and the Cetuximab was covalently modified with transcyclooctene (TCO-NHS). The stability of 99mTc-HYNIC-Polypeptide-PEG11-Tz was evaluated in vitro, and its blood pharmacokinetic test was performed in vivo. Determination of the n-octanol/PBS distribution coefficient was performed on 99mTc-HYNIC-PEG11-Tz and 99mTc-HYNIC-Polypeptide-PEG11-Tz to determine the effect of linker modification on their hydrophobicity. In vitro ligation reactivity of 99mTc-HYNIC-Polypeptide-PEG11-Tz towards Cetuximab-TCO was tested. Pretargeted HCT116 cell immunoreactivity binding assay was evaluated. The biodistribution and imaging of 99mTc-HYNIC-Polypeptide-PEG11-Tz was performed to observe the clear pathway of this novel Tz-radioligand. Pretargeted biodistribution of three different accumulation intervals (24 h, 48 h, and 72 h) was performed to determine the optimal pretargeted interval time in nude mice bearing HCT116 tumor xenografts. Comparison of pretargeted (Cetuximab-TCO 48h/99mTc-HYNIC-PEG11-Tz 6h) and (Cetuximab-TCO 48h/ 99mTc-HYNIC-Polypeptide-PEG11-Tz 6h) imaging was performed to show the effect of the two Tz-radioligands with different excretion pathway on tumor imaging. Results: HYNIC-Polypeptide-PEG11-Tz was successfully radiosynthesized with 99mTc, and a radiochemical purity greater than 95% were obtained as confirmed by radio high-performance liquid chromatography (HPLC). 99mTc-HYNIC-Polypeptide-PEG11-Tz showed favorable stability in NS, PBS, and FBS and rapid blood clearance in mice. Liquid chromatograph-mass spectrometer (LC-MS) indicated the presence of an average 8.1 TCO moieties per Cetuximab. Size exclusion HPLC revealed almost complete reaction between Cetuximab-TCO and 99mTc-HYNIC-Polypeptide-PEG11-Tz in vitro, with the 8:1 Tz-to-mAb reaction providing a conversion yield of 87.83±3.27%. Pretargeted cell immunoreactivity binding assay showed high affinity to HCT116 cells. The biodistribution and imaging of 99mTc-HYNIC-Polypeptide-PEG11-Tz demonstrated that the Tz-radioligand was cleared through kidneys. After allowing 24h, 48h and 72h for accumulation of Cetuximab-TCO in HCT116 tumor, pretargeted biodistribution revealed an uptake of the radiotracer in the tumor with tumor-to-blood ratio of 0.83, 1.40, and 1.15, respectively. Both pretargeted (Cetuximab-TCO 48h/99mTc-HYNIC-PEG11-Tz 6h) and (Cetuximab-TCO 48h/ 99mTc-HYNIC-Polypeptide-PEG11-Tz 6h) imaging delineated the HCT116 tumor clearly. However, pretargeted imaging strategy using Cetuximab-TCO 48h/99mTc-HYNIC-Polypeptide-PEG11-Tz 6h) could be used for diagnosing colorectal cancer since the surplus unclicked 99mTc-HYNIC-Polypeptide-PEG11-Tz is cleared through urinary system and produces low abdominal uptake background. Conclusion: We developed a novel pretargeted imaging strategy (Cetuximab-TCO/99mTc-HYNIC-Polypeptide-PEG11-Tz) for imaging colorectal cancer since the surplus unclicked 99mTc-HYNIC-Polypeptide-PEG11-Tz produces low abdominal uptake background, which broadens the application scope of pretargeted imaging strategy.

Patients with fever of unknown origin (FUO): diagnosis by nuclear medicine imaging

2001 ◽  
Vol 40 (03) ◽  
pp. 59-70 ◽  
Author(s):  
W. Becker ◽  
J. Meiler
Keyword(s):  
Nuclear Medicine ◽  
Fever Of Unknown Origin ◽  
Tumor Imaging ◽  
White Blood Cells ◽  
Unknown Origin ◽  
Final Diagnosis ◽  
Recurrent Fever ◽  
Nuclear Medicine Imaging

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.

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

2019 ◽  
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 [<sup>18</sup>F]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 [<sup>18</sup>F]fluorosulfate based PET agents enabled by the emerging sulfur fluoride exchange (SuFEx) click chemistry. The method has been applied to the fully-automated <sup>18</sup>F-radiolabeling of twenty-five structurally diverse aryl fluorosulfates with excellent radiochemical yield (83–100%) and high molar activity (up to 281 GBq µmol<sup>–1</sup>) 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 [<sup>18</sup>F]fluorosulfate is demonstrated by the <i>in vivo</i> tumor imaging by targeting poly(ADP-ribose) polymerase 1 (PARP1).

Natural Killer Cell Inspired AIE Nanoterminator for Blood-Brain-Barrier Crossing via Tight-Junction Modulation and NIR-II Gliomas Theranostics

2020 ◽  
Author(s):  
Guanjun Deng ◽  
Xinghua Peng ◽  
Zhihong Sun ◽  
Wei Zheng ◽  
Jia Yu ◽  
...  
Keyword(s):  
Natural Killer Cell ◽  
Natural Killer ◽  
Intracellular Signaling ◽  
Soft Matter ◽  
Tumor Imaging ◽  
Nk Cell ◽  
Killer Cell ◽  
Light Illumination ◽  
Blood Brain ◽  
Intracellular Signaling Cascade

Nature has always inspired robotic designs and concepts. It is conceivable that biomimic nanorobots will soon play a prominent role in medicine. In this paper, we developed a natural killer cell-mimic AIE nanoterminator (NK@AIEdots) by coating natural kill cell membrane on the AIE-active polymeric endoskeleton, PBPTV, a highly bright NIR-II AIE-active conjugated polymer. Owning to the AIE and soft-matter characteristics of PBPTV, as-prepared nanoterminator maintained the superior NIR-II brightness (quantum yield ~8%) and good biocompatibility. Besides, they could serve as tight junctions (TJs) modulator to trigger an intracellular signaling cascade, causing TJs disruption and actin cytoskeleton reorganization to form intercellular “green channel” to help themselves crossing Blood-Brain Barriers (BBB) silently. Furthermore, they could initiatively accumulate to glioblastoma cells in the complex brain matrix for high-contrast and through-skull tumor imaging. The tumor growth was also greatly inhibited by these nanoterminator under the NIR light illumination. As far as we known, The QY of PBPTV is the highest among the existing NIR-II luminescent conjugated polymers. Besides, the NK-cell biomimetic nanorobots will open new avenue for BBB-crossing delivery.

Evaluation and treatment of children with radiation-induced cerebral vasculopathy

2019 ◽  
Vol 24 (6) ◽  
pp. 680-688
Author(s):  
David S. Hersh ◽  
Kenneth Moore ◽  
Vincent Nguyen ◽  
Lucas Elijovich ◽  
Asim F. Choudhri ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Proton Beam ◽  
Tumor Imaging ◽  
Clinic Visit ◽  
Surgical Patient ◽  
Beam Radiation ◽  
Proton Beam Radiotherapy ◽  
Cranial Radiation ◽  
Delayed Complication ◽  
Radiation Induced

OBJECTIVEStenoocclusive cerebral vasculopathy is an infrequent delayed complication of ionizing radiation. It has been well described with photon-based radiation therapy but less so following proton-beam radiotherapy. The authors report their recent institutional experience in evaluating and treating children with radiation-induced cerebral vasculopathy.METHODSEligible patients were age 21 years or younger who had a history of cranial radiation and subsequently developed vascular narrowing detected by MR arteriography that was significant enough to warrant cerebral angiography, with or without ischemic symptoms. The study period was January 2011 to March 2019.RESULTSThirty-one patients met the study inclusion criteria. Their median age was 12 years, and 18 (58%) were male. Proton-beam radiation therapy was used in 20 patients (64.5%) and photon-based radiation therapy was used in 11 patients (35.5%). Patients were most commonly referred for workup as a result of incidental findings on surveillance tumor imaging (n = 23; 74.2%). Proton-beam patients had a shorter median time from radiotherapy to catheter angiography (24.1 months [IQR 16.8–35.4 months]) than patients who underwent photon-based radiation therapy (48.2 months [IQR 26.6–61.1 months]; p = 0.04). Eighteen hemispheres were revascularized in 15 patients. One surgical patient suffered a contralateral hemispheric infarct 2 weeks after revascularization; no child treated medically (aspirin) has had a stroke to date. The median follow-up duration was 29.2 months (IQR 21.8–54.0 months) from the date of the first catheter angiogram to last clinic visit.CONCLUSIONSAll children who receive cranial radiation therapy from any source, particularly if the parasellar region was involved and the child was young at the time of treatment, require close surveillance for the development of vasculopathy. A structured and detailed evaluation is necessary to determine optimal treatment.

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