Article
Biochemistry & Molecular Biology
Vladimir Tolmachev, Vitalina Bodenko, Maryam Oroujeni, Sergey Deyev, Elena Konovalova, Alexey Schulga, Sarah Lindbo, Sophia Hober, Olga Bragina, Anna Orlova, Anzhelika Vorobyeva
Summary: Non-invasive radionuclide molecular visualization of human epidermal growth factor receptor type 2 (HER2) provides stratification and response monitoring for HER2-targeting therapy. Two imaging probes, [Tc-99m]Tc-ADAPT6 and [Tc-99m]Tc-(HE)(3)-G3, demonstrate high contrast imaging and clear discrimination of high and low HER2 expression. However, [Tc-99m]Tc-ADAPT6 has better conditions for stratification sensitivity and specificity, while [Tc-99m]Tc-(HE)(3)-G3 is more suitable for monitoring early treatment response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Analytical
Sumeera Sidiq, Ravi Ranjan Kumar, Neelima D. Passi, D. K. Dhawan, Jaya Shukla, B. R. Mittal, Vijayta D. Chadha
Summary: The study demonstrated that [Tc-99m]Tc-GSH has a high radiochemical yield and good binding capability in HT 29 colon cancer cell line, while showing no toxicity to the cells. Both in vitro and in vivo results suggest that the radiocomplex has tumor delineating features and selectivity for colon tumor.
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
(2021)
Article
Oncology
Javad Biabani Ardakani, Seyed Mohammad Abedi, Alireza Mardanshahi, Leyla Shojaee, Ehsan Zaboli, Alireza Khorramimoghaddam, Anahita Nosrati, Hamideh Sabahno, Elahm Sadat Banimostafavi, Seyed Jalal Hosseinimehr
Summary: The accurate determination of HER2 status can predict response to treatment with HER2-targeted therapy for HER2-positive breast cancer. In this study, a new Tc-99m radiolabeled peptide was used to detect HER2 status in primary tumors, and the findings corresponded with immunohistochemistry results of tumor samples.
CLINICAL BREAST CANCER
(2023)
Review
Chemistry, Multidisciplinary
Sajid Mushtaq, Asia Bibi, Jung Eun Park, Jongho Jeon
Summary: Nanotechnology has made significant contributions to molecular imaging and cancer therapy, but there is still a gap between preclinical products and clinically approved drugs. Effective translation of preclinical results to clinical settings requires critical studies such as detailed pharmacokinetics and biodistribution research and efficient drug delivery to target organs.
Article
Oncology
Olga Bragina, Vladimir Chernov, Alexey Schulga, Elena Konovalova, Sophia Hober, Sergey Deyev, Jens Sorensen, Vladimir Tolmachev
Summary: The overexpression of HER2 receptor in certain breast cancers can be successfully treated with trastuzumab and pertuzumab antibodies. Radionuclide imaging can assist in selecting patients for antibody treatment. The small-sized radiolabelled scaffold proteins ADAPT6 and DARPin have shown excellent imaging properties and promising results in the imaging of HER2 in preclinical and Phase I clinical trials.
Article
Pharmacology & Pharmacy
Masayuki Munekane, Asami Kosugi, Mizuho Yamasaki, Yoko Watanabe, Kento Kannaka, Kohei Sano, Toshihide Yamasaki, Ken-ichi Ogawara, Takahiro Mukai
Summary: This study investigates the application of niosomes composed of non-ionic surfactants as drug carriers, and concludes that PEGylated niosomes can serve as tumor-targeting drug carriers.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2022)
Article
Medicine, Research & Experimental
Yuhao Jiang, Si'an Fang, Junhong Feng, Qing Ruan, Junbo Zhang
Summary: To find a new radiotracer for SPECT imaging of bacterial infection with reduced uptake in non-target organs, a novel norfloxacin derivative (HYNICNF) was synthesized and labeled with 99mTc using different coligands. The labeled complexes showed good stability, hydrophilicity, and specific binding to Staphylococcus aureus in vitro. In vivo biodistribution studies in mice with bacterial infection demonstrated that [99mTc]Tc-EDDA-HYNICNF exhibited higher abscess uptake, lower nontarget organ uptake, and the ability to differentiate bacterial infection from sterile inflammation. SPECT imaging in bacterial infection mice confirmed visible accumulation at the infection site, suggesting that [99mTc]Tc-EDDA-HYNICNF is a potential radiotracer for bacterial infection imaging.
MOLECULAR PHARMACEUTICS
(2023)
Article
Chemistry, Inorganic & Nuclear
George Makris, Yawen Li, Fabio Gallazzi, Marina Kuchuk, Jing Wang, Michael R. Lewis, Silvia S. Jurisson, Heather M. Hennkens
Summary: This study synthesized Tc-99m/Re (radio)complexes for potential application in diagnostic imaging and therapy of neuroendocrine tumors. The compounds showed high binding affinity and good stability in vitro.
Article
Chemistry, Medicinal
Qing Ruan, Qianqian Gan, Xuran Zhang, Si'an Fang, Junbo Zhang
Summary: Novel Tc-99m-labeled single-photon emission computed tomography (SPECT) radiotracers were developed for hypoxia imaging using a newly designed HYNICNM ligand. The radiolabeled complexes exhibited good hypoxic selectivity and high tumor uptake, especially for [Tc-99m]Tc-tricine-TPPTS-HYNICNM, which showed promising potential as an imaging agent for tumor hypoxia.
Article
Chemistry, Medicinal
Junhong Feng, Xuran Zhang, Yuhao Jiang, Qing Ruan, Qianna Wang, Junbo Zhang
Summary: To develop effective tumor imaging agents, a glucose derivative containing cyclohexane was synthesized and labeled with Tc-99m. The labeled compound showed high purity, stability, and hydrophilicity. Cellular studies suggested that the compound's uptake was affected by glucose and insulin, potentially through GLUTs. Biodistribution and imaging studies in tumor-bearing mice demonstrated high tumor uptake, good retention, and promising clinical potential.
Article
Chemistry, Medicinal
Di Xiao, Yuhao Jiang, Junhong Feng, Qing Ruan, Qianna Wang, Guangxing Yin, Junbo Zhang
Summary: Novel bone imaging agents were developed by synthesizing bisphosphonate isocyanide derivatives and radiolabeling them with Tc-99m. The [Tc-99m] Tc-CNALN complex showed high stability and bone/background ratio, making it a promising bone-seeking agent.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Medicine, Research & Experimental
Shahnaz Saednia, Saeed Emami, Sajjad Molavipordanjani, Seyed Mohammad Abedi, Fereshteh Talebpour Amiri, Seyed Jalal Hosseinimehr
Summary: This study aimed to develop novel tracers for targeting and imaging overexpressed serotonin-7 receptors in U-87 MG glioma xenografted nude mice. The radiotracers Tc-99m-PHH and Tc-99m-MPHH showed promising affinity and uptake in the tumor tissue, with Tc-99m-MPHH demonstrating higher affinity to 5-HT7Rs.
MOLECULAR PHARMACEUTICS
(2021)
Article
Biology
Noha A. Bayoumi, Ahmed N. Emam
Summary: Carbon dots (CDs) have gained attention as a tumor targeting agent due to their favorable physicochemical properties and biocompatibility. Polyethylenimine capped CDs were successfully synthesized as a potential nanocarrier for Technetium-99m (Tc-99m) with promising tumor targeting efficiency. Tc-99m-labeled PEI capped CDs showed potential as a SPECT tumor imaging agent with high tumor uptake and target to non-target ratio.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Amit Kumar Sharma, Drishty Satpati, Rohit Sharma, Amit Das, Haladhar Dev Sarma, Archana Mukherjee
Summary: In this study, a click reaction catalyzed by on-resin Cu(I) was performed to synthesize triazole-stapled cyclic peptide mimetic, DOTA-c[TZ]A9, targeting HER2 receptor expression in breast cancers. Spectroscopic and docking analysis showed that the triazole-stapled peptide exhibited enhanced helicity, secondary structure stabilization, and improved HER2 affinity compared to the linear peptide, DOTA-[Pra1, Aza7]A9. Biodistribution studies in tumor-bearing mice demonstrated higher radioactivity levels and prolonged retention of the cyclic peptide in the tumor compared to the linear peptide.
BIOORGANIC CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Olga Bragina, Vladimir Chernov, Mariia Larkina, Anstasiya Rybina, Roman Zelchan, Eugeniy Garbukov, Maryam Oroujeni, Annika Loftenius, Anna Orlova, Jens Soerensen, Fredrik Y. Frejd, Vladimir Tolmachev
Summary: The determination of tumor HER2 status is crucial for HER2-targeted treatments. This study evaluated the safety and dosimetry of Tc-99m-ZHER2:41071 Affibody molecule for SPECT/CT imaging of HER2 expression. The results showed that the injection of Tc-99m-ZHER2:41071 was safe and provided effective discrimination between HER2-positive and HER2-low/negative tumors.
Article
Radiology, Nuclear Medicine & Medical Imaging
Olga Bragina, Vladimir Chernov, Alexey Schulga, Elena Konovalova, Eugeniy Garbukov, Anzhelika Vorobyeva, Anna Orlova, Liubov Tashireva, Jens Sorensen, Roman Zelchan, Anna Medvedeva, Sergey Deyev, Vladimir Tolmachev
Summary: The study evaluated the safety, biodistribution, and dosimetry of Tc-99m-(HE)(3)-G3 in breast cancer patients, showing that the imaging method provides a low absorbed dose burden on patients and is safe and well-tolerated.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Tianqi Xu, Jie Zhang, Maryam Oroujeni, Maria S. Tretyakova, Vitalina Bodenko, Mikhail Belousov, Anna Orlova, Vladimir Tolmachev, Anzhelika Vorobyeva, Torbjorn Graslund
Summary: This study investigated the influence of linker length and composition on the functionality and biodistribution of targeted drug conjugates, finding that longer linkers decreased affinity to HER2 and serum albumin but reduced liver uptake. This provides important insights into molecular design for developing drug conjugates with reduced hepatic uptake.
Article
Pharmacology & Pharmacy
Vladimir Chernov, Ekaterina Dudnikova, Roman Zelchan, Anna Medvedeva, Anstasiya Rybina, Olga Bragina, Viktor Goldberg, Albina Muravleva, Jens Sorensen, Vladimir Tolmachev
Summary: This study evaluated the safety, biodistribution, and dosimetry of [Tc-99m]Tc-TG in lymphoma patients, and found that it can be considered as an additional diagnostic method for imaging GLUT receptors in these patients.
Article
Biochemistry & Molecular Biology
Tianqi Xu, Alexey Schulga, Elena Konovalova, Sara S. Rinne, Hongchao Zhang, Olga Vorontsova, Anna Orlova, Sergey M. Deyev, Vladimir Tolmachev, Anzhelika Vorobyeva
Summary: Pancreatic cancer (PC) is an aggressive malignancy, and targeted therapies could improve its treatment. Overexpression of HER3 and EpCAM in PC is associated with poor prognosis. The study investigated whether co-targeting HER3 with MM-121 and EpCAM with Ec1-LoPE could enhance therapeutic efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Fanny Lundmark, Ayman Abouzayed, Sara S. S. Rinne, Vasiliy Timofeev, Nadezhda Sipkina, Maria Naan, Anastasia Kirichenko, Maria Vasyutina, Daria Ryzhkova, Vladimir Tolmachev, Ulrika Rosenstrom, Anna Orlova
Summary: Prostate cancer is the most diagnosed cancer and leading cause of cancer-related deaths in men. This study presents the preclinical characterization and evaluation of a radiotracer that targets both PSMA and GRPR for PET imaging of prostate cancer. The findings support the clinical translation of the radiotracer and represent a step towards its first clinical trial.
Article
Oncology
Yongsheng Liu, Tianqi Xu, Anzhelika Vorobyeva, Annika Loftenius, Vitalina Bodenko, Anna Orlova, Fredrik Y. Frejd, Vladimir Tolmachev
Summary: Affibody molecules are artificial proteins that can target cancer-related molecular abnormalities. Clinical studies have shown that they can be used for radionuclide diagnostics and therapy. This study demonstrated that re-engineered Affibody molecules can increase the survival of mice with human tumors, and the combination of Affibody molecules and a monoclonal antibody was the most effective treatment.
Article
Oncology
Olga Bragina, Vladimir Chernov, Alexey Schulga, Elena Konovalova, Sophia Hober, Sergey Deyev, Jens Sorensen, Vladimir Tolmachev
Summary: The overexpression of HER2 receptor in certain breast cancers can be successfully treated with trastuzumab and pertuzumab antibodies. Radionuclide imaging can assist in selecting patients for antibody treatment. The small-sized radiolabelled scaffold proteins ADAPT6 and DARPin have shown excellent imaging properties and promising results in the imaging of HER2 in preclinical and Phase I clinical trials.
Article
Medicine, General & Internal
Ayman Abouzayed, Jesper Borin, Fanny Lundmark, Anastasiya Rybina, Sophia Hober, Roman Zelchan, Vladimir Tolmachev, Vladimir Chernov, Anna Orlova
Summary: A kit was successfully prepared for prospective use in an early-phase clinical study, allowing for one-pot single-step radiolabeling with technetium-99m. The radiolabeled peptide maintained its binding properties and showed good safety in animal models after 18 months of storage. Therefore, the prepared kit can be further evaluated for clinical application.
Article
Biochemistry & Molecular Biology
Ayman Abouzayed, Panagiotis Kanellopoulos, Alisa Gorislav, Vladimir Tolmachev, Theodosia Maina, Berthold A. Nock, Anna Orlova
Summary: This study presents a new GRPR antagonist with improved stability and specificity for the theranostics of prostate cancer. In vitro and in vivo experiments showed that the new compound demonstrated higher stability and selective targeting, indicating its potential therapeutic value.
Article
Medicine, General & Internal
O. D. Bragina, S. M. Deyev, E. Yu Garbukov, V. E. Goldberg, V. I. Chernov, V. M. Tolmachev
Summary: This study compared the diagnostic efficacy of two diagnostic agents, [(99)mTc]Tc-ADAPT6 and [(99)mTc]Tc-(HE)3-G3, in HER2-positive breast cancer patients. The results showed that [(99)mTc]Tc-ADAPT6 had higher accumulation values, making it a more promising diagnostic agent.
BYULLETEN SIBIRSKOY MEDITSINY
(2023)