scholarly journals Synthesis and evaluation of novel F-18-labeled pyrimidine derivatives: potential FAK inhibitors and PET imaging agents for cancer detection

RSC Advances ◽  
2017 ◽  
Vol 7 (36) ◽  
pp. 22388-22399 ◽  
Author(s):  
Dawei Wang ◽  
Yu Fang ◽  
Hang Wang ◽  
Xingyu Xu ◽  
Jianping Liu ◽  
...  
Keyword(s):  
Cancer Detection ◽  
Pet Imaging ◽  
Imaging Study ◽  
Imaging Agents ◽  
Post Injection ◽  
Pyrimidine Derivatives ◽  
Micropet Imaging ◽  
Tumor Bearing ◽  
Biodistribution Data

Compound [18F]-8a exhibited good in vivo biodistribution data in mice bearing S180 tumor. And the microPET imaging study of [18F]-8a in S180 tumor-bearing mice was also preformed, which illustrated that the uptake in S180 tumor at 60 min post-injection of [18F]-8a was obvious.

Evaluation of New 99mTc(CO)3 + Radiolabeled Glycylglycine In Vivo

2019 ◽  
Vol 19 (11) ◽  
pp. 1382-1387
Author(s):  
Ahmet M. Şenışık ◽  
Çiğdem İçhedef ◽  
Ayfer Y. Kılçar ◽  
Eser Uçar ◽  
Kadir Arı ◽  
...  
Keyword(s):  
High Performance ◽  
The Body ◽  
Biological Behavior ◽  
In Vivo Evaluation ◽  
Radiolabeled Peptides ◽  
Tumor Bearing ◽  
Biodistribution Data ◽  
Good Accordance ◽  
Rapid Clearance

Background: Peptide-based agents are used in molecular imaging due to their unique properties, such as rapid clearance from the circulation, high affinity and target selectivity. Many of the radiolabeled peptides have been clinically experienced with diagnostic accuracy. The aim of this study was to investigate in vivo biological behavior of [99mTc(CO)3(H2O)3]+ radiolabeled glycylglycine (GlyGly). Methods: Glycylglycine was radiolabeled with a high radiolabeling yield of 94.69±2%, and quality control of the radiolabeling process was performed by thin layer radiochromatography (TLRC) and High-Performance Liquid Radiochromatography (HPLRC). Lipophilicity study for radiolabeled complex (99mTc(CO)3-Gly-Gly) was carried out using solvent extraction. The in vivo evaluation was performed by both biodistribution and SPECT imaging. Results: The high radiolabelling yield of 99mTc(CO)3-GlyGly was obtained and verified by TLRC and HPLRC as well. According to the in vivo results, SPECT images and biodistribution data are in good accordance. The excretion route from the body was both hepatobiliary and renal. Conclusion: This study shows that 99mTc(CO)3-GlyGly has the potential to be used as a peptide-based imaging agent. Further studies, 99mTc(CO)3-GlyGly can be performed on tumor-bearing animals.

64Cu-PSMA-BCH: A New Radiotracer for Delayed PET Imaging of Prostate Cancer

2021 ◽  
Author(s):  
Teli Liu ◽  
Chen Liu ◽  
Zhongyi Zhang ◽  
Ning Zhang ◽  
Xiaoyi Guo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Pet Imaging ◽  
Radiation Dosimetry ◽  
Whole Body ◽  
Post Injection ◽  
Human Organ ◽  
Fine Needle ◽  
Fine Needle Aspirates ◽  
Psma Pet

Abstract PurposeDevelop a 64Cu labeled radiopharmaceutical targeting prostate specific membrane antigen (PSMA) and investigate its application for prostate cancer imaging. Methods64Cu-PSMA-BCH was prepared and investigated for stability, PSMA specificity and micro-PET imaging. With the approval of Ethics Committee of Beijing Cancer Hospital (No. 2017KT97), PET/CT imaging in 4 patients with suspected prostate cancer was performed and the radiation dosimetry was estimated. Then, PSMA PET-ultrasound image-guided biopsies were performed on 3 patients and the fine needle aspirates were further performed for autoradiography and immunohistochemistry analysis. Results64Cu-PSMA-BCH was prepared with high radiochemical yield and stability. In vivo study showed higher uptake in PSMA (+) 22Rv1 cells than PSMA (-) PC-3 cells (5.59±0.36 and 1.97±0.22 IA%/106 cells at 1 h). It accumulated in 22Rv1 tumor with increasing radioactivity uptake and T/N ratios from 1 h to 24 h post-injection. In patients with suspected prostate cancer, SUVmax and T/N ratios increased within 24 h post-injection. Compared with image at 1 h post-injection, more tumor lesions were detected at 4 h and 24 h post-injection. The human organ radiation dosimetry showed gallbladder wall was most critical, liver and kidneys were followed, and the whole-body effective dose was 0.0292 mSv/MBq. Two fine needle aspirates obtained by PET-ultrasound guided targeted biopsy showed high radioactive signal by autoradiography, with 100% PSMA expression in cytoplasm and 30% expression in nucleus. Conclusion64Cu-PSMA-BCH was PSMA specific and showed high stability in vivo with lower uptake in liver than 64Cu-PSMA-617. Biodistribution in mice and PCa patients showed similar profile compared with other PSMA ligands and it was safe with moderate effective dosimetry. The increased tumor uptake and T/N ratios by delayed imaging may facilitate the detection of small lesions and guiding targeted biopsies.

scholarly journals F-18 Labeled Vasoactive Intestinal Peptide Analogue in the PET Imaging of Colon Carcinoma in Nude Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Dengfeng Cheng ◽  
Yuxia Liu ◽  
Hua Shen ◽  
Lifang Pang ◽  
Duanzhi Yin ◽  
...  
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Colon Carcinoma ◽  
Pet Imaging ◽  
Specific Activity ◽  
Imaging Study ◽  
Radiochemical Yield ◽  
Receptor Imaging ◽  
Improved Stability ◽  
Vip Receptor

As large amount of vasoactive intestinal peptide (VIP) receptors are expressed in various tumors and VIP-related diseases, radiolabeled VIP provides a potential PET imaging agent for VIP receptor. However, structural modification of VIP is required before being radiolabeled and used for VIP receptor imaging due to its poor in vivo stability. As a VIP analogue, [R8, 15, 21, L17]-VIP exhibited improved stability and receptor specificity in preliminary studies. In this study, F-18 labeled [R8,15,21, L17]-VIP was produced with the radiochemical yield being as high as33.6%±3%(decay-for-corrected,n=5) achieved within 100 min, a specific activity of 255 GBq/μmol, and a radiochemical purity as high as 99% as characterized by radioactive HPLC, TLC, and SDS-Page radioautography. A biodistribution study in normal mice also demonstrated fast elimination of F-18 labeled [R8,15,21, L17]-VIP in the blood, liver, and gastrointestinal tracts. A further micro-PET imaging study in C26 colon carcinoma bearing mice confirmed the high tumor specificity, with the tumor/muscle radioactivity uptake ratio being as high as 3.03 at 60 min following injection, and no apparent radioactivity concentration in the intestinal tracts. In addition, blocking experiment and Western Blot test further confirmed its potential in PET imaging of VIP receptor-positive tumor.

scholarly journals Thiol-Reactive PODS-Bearing Bifunctional Chelators for the Development of EGFR-Targeting [18F]AlF-Affibody Conjugates

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1562
Author(s):  
Chiara Da Pieve ◽  
Ata Makarem ◽  
Stephen Turnock ◽  
Justyna Maczynska ◽  
Graham Smith ◽  
...  
Keyword(s):  
Radiochemical Yield ◽  
Post Injection ◽  
Bifunctional Chelators ◽  
Tumor Bearing ◽  
Specific Tumor ◽  
Thiol Reaction ◽  
Site Selective ◽  
In Vitro Stability

Site-selective bioconjugation of cysteine-containing peptides and proteins is currently achieved via a maleimide–thiol reaction (Michael addition). When maleimide-functionalized chelators are used and the resulting bioconjugates are subsequently radiolabeled, instability has been observed both during radiosynthesis and post-injection in vivo, reducing radiochemical yield and negatively impacting performance. Recently, a phenyloxadiazolyl methylsulfone derivative (PODS) was proposed as an alternative to maleimide for the site-selective conjugation and radiolabeling of proteins, demonstrating improved in vitro stability and in vivo performance. Therefore, we have synthesized two novel PODS-bearing bifunctional chelators (NOTA-PODS and NODAGA-PODS) and attached them to the EGFR-targeting affibody molecule ZEGFR:03115. After radiolabeling with the aluminum fluoride complex ([18F]AlF), both conjugates showed good stability in murine serum. When injected in high EGFR-expressing tumor-bearing mice, [18F]AlF-NOTA-PODS-ZEGFR:03115 and [18F]AlF-NODAGA-PODS-ZEGFR:03115 showed similar pharmacokinetics and a specific tumor uptake of 14.1 ± 5.3% and 16.7 ± 4.5% ID/g at 1 h post-injection, respectively. The current results are encouraging for using PODS as an alternative to maleimide-based thiol-selective bioconjugation reactions.

A Comparative Study of in vitro Assays for Predicting the Nonspecific Binding of PET Imaging Agents in vivo

ChemMedChem ◽  
2019 ◽  
Vol 15 (7) ◽  
pp. 585-592
Author(s):  
Luca Gobbi ◽  
Joël Mercier ◽  
Benny Bang‐Andersen ◽  
Jean‐Marie Nicolas ◽  
John Reilly ◽  
...  
Keyword(s):  
Comparative Study ◽  
Pet Imaging ◽  
In Vitro Assays ◽  
Imaging Agents ◽  
Nonspecific Binding

99mTc-citrate-gold nanoparticles as a tumor tracer: synthesis, characterization, radiolabeling and in-vivo studies

2020 ◽  
Vol 108 (10) ◽  
pp. 809-819 ◽  
Author(s):  
Basma M. Essa ◽  
Ahmed A. El-Mohty ◽  
Maher A. El-Hashash ◽  
Tamer M. Sakr
Keyword(s):  
Drug Delivery ◽  
Gold Nanoparticles ◽  
Drug Delivery System ◽  
Delivery System ◽  
Solid Tumor ◽  
Tumor Imaging ◽  
In Vivo Studies ◽  
Post Injection ◽  
Tumor Bearing

AbstractTargeted drug delivery system can reduce the side effects of high drug concentration by improving drug pharmacokinetics at lower doses. Citrate-gold nanoparticles (AuNPs) as a drug delivery system were synthesized via green nanotechnology technique to be used as a new imaging platform for tumor targeting. Citrate-AuNPs were synthesized with core size of 10 nm. Citrate-AuNPs were labeled with technetium-99m (99mTc) with radiochemical yield of 95.20 ± 2.70% with good in-vitro stability in both saline and human serum and well in-vivo studied in both normal and solid tumor bearing mice. The in-vivo biodistribution study of [99mTc]Tc-citrate-AuNPs in solid tumor bearing mice (as preliminary study) showed a high accumulation in tumor site with tumor/muscle of 4.35 ± 0.22 after 30 min post injection. The direct intratumoral (I.T) injection of [99mTc]Tc-citrate-AuNPs showed that this complex was retained in the tumor up to 77.86 ± 1.90 % at 5 min and still around 50.00 ± 1.42 % after 30 min post injection (p.i.). The newly presented nano-platform could be presented as a new potential radiopharmaceutical tumor imaging probe.

scholarly journals The Use of a Non-Conventional Long-Lived Gallium Radioisotope 66Ga Improves Imaging Contrast of EGFR Expression in Malignant Tumours Using DFO-ZEGFR:2377 Affibody Molecule

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 292 ◽  
Author(s):  
Maryam Oroujeni ◽  
Tianqi Xu ◽  
Katherine Gagnon ◽  
Sara S. Rinne ◽  
Jan Weis ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Growth Factor Receptor ◽  
Whole Body ◽  
Malignant Tumours ◽  
Affibody Molecule ◽  
Egfr Expression ◽  
Biodistribution Data ◽  
Positron Emitter

Epidermal growth factor receptor (EGFR) is overexpressed in many malignancies. EGFR-targeted therapy extends survival of patients with disseminated cancers. Radionuclide molecular imaging of EGFR expression would make EGFR-directed treatment more personalized and therefore more efficient. A previous study demonstrated that affibody molecule [68Ga]Ga-DFO-ZEGFR:2377 permits specific positron-emission tomography (PET) imaging of EGFR expression in xenografts at 3 h after injection. We anticipated that imaging at 24 h after injection would provide higher contrast, but this is prevented by the short half-life of 68Ga (67.6 min). Here, we therefore tested the hypothesis that the use of the non-conventional long-lived positron emitter 66Ga (T1/2 = 9.49 h, β+ = 56.5%) would permit imaging with higher contrast. 66Ga was produced by the 66Zn(p,n)66Ga nuclear reaction and DFO-ZEGFR:2377 was efficiently labelled with 66Ga with preserved binding specificity in vitro and in vivo. At 24 h after injection, [66Ga]Ga-DFO-ZEGFR:2377 provided 3.9-fold higher tumor-to-blood ratio and 2.3-fold higher tumor-to-liver ratio than [68Ga]Ga-DFO-ZEGFR:2377 at 3 h after injection. At the same time point, [66Ga]Ga-DFO-ZEGFR:2377 provided 1.8-fold higher tumor-to-blood ratio, 3-fold higher tumor-to-liver ratio, 1.9-fold higher tumor-to-muscle ratio and 2.3-fold higher tumor-to-bone ratio than [89Zr]Zr-DFO-ZEGFR:2377. Biodistribution data were confirmed by whole body PET combined with magnetic resonance imaging (PET/MRI). The use of the positron emitter 66Ga for labelling of DFO-ZEGFR:2377 permits PET imaging of EGFR expression at 24 h after injection and improves imaging contrast.

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