Gold-containing nanoparticles are proven to be an effective radiosensitizer in the radiotherapy of tumors. Reliable imaging of nanoparticles in a tumor and surrounding normal tissues is crucial both for diagnostics and for nanoparticle application as radiosensitizers. The Fe3O4 core was introduced into gold nanoparticles to form a core/shell structure suitable for MRI imaging. The aim of this study was to assess the in vivo bimodal CT and MRI enhancement ability of novel core/shell Fe3O4@Au theranostic nanoparticles. Core/shell Fe3O4@Au nanoparticles were synthesized and coated with PEG and glucose. C57Bl/6 mice bearing Ca755 mammary adenocarcinoma tumors received intravenous injections of the nanoparticles. CT and MRI were performed at several timepoints between 5 and 102 min, and on day 17 post-injection. Core/shell Fe3O4@Au nanoparticles provided significant enhancement of the tumor and tumor blood vessels. Nanoparticles also accumulated in the liver and spleen and were retained in these organs for 17 days. Mice did not show any signs of toxicity over the study duration. These results indicate that theranostic bimodal Fe3O4@Au nanoparticles are non-toxic and serve as effective contrast agents both for CT and MRI diagnostics. These nanoparticles have potential for future biomedical applications in cancer diagnostics and beyond.
In this work, a series of boronated amidines based on the closo-dodecaborate anion and amino acids containing an amino group in the side chain of the general formula [B12H11NHC(NH(CH2)nCH(NH3)COOH)CH3], where n = 2, 3, 4, were synthesized. These derivatives contain conserved α-amino and α-carboxyl groups recognized by the binding centers of the large neutral amino acid transporter (LAT) system, which serves as a target for the clinically applied BNCT agent para-boronophenylalanine (BPA). The paper describes several approaches to synthesizing the target compounds, their acute toxicity studies, and tumor uptake studies in vivo in two tumor models. The promising compound [B12H11NHC(NH(CH2)2CH(NH3)COOH)CH3]*3H2O demonstrates low toxicity (LD50 in a range from 150 to 300 mg/kg) and excellent solubility and also shows selective uptake in experimental melanoma in laboratory mice (T/N ratio remained >3 up to 60 min post-injection, with a maximum T/N of 6.2 ± 2.8 at 45 min).
The object of the study was to analyze radionuclide detection techniques for in vivo animal imaging. Material and Methods. A total of 49 publications available from Scopus, Web of Science, Google Scholar eLIBRARY and Pubmed and published between 2013 and 2019 were reviewed. Results. The nuclear medicine techniques, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) are the most suitable imaging modalities for in vivo animal imaging. Besides traditional radiopharmaceuticals, such as [18F]-FDG and [99mTc]-MDP, the new radiolabeled tracers, such as [99mTc]-3PRGD2, [ 99mTc]-HisoDGR targeted to integrin, [18F]- tetrafluoroborate, labeled antibodies and others have been used for the noninvasive detection of tumors and for monitoring their response to treatment in mice and rats. 111In and 89Zr –labeled monoclonal antibodies are used to evaluate the expression level of many receptors such as EGFR, HER-2 and others in different tumors. PET imaging has demonstrated a good efficacy in tumor hypoxia imaging with [64Cu]-ATSM, [18F]-FMISO. PET and SPECT can also be used for early evaluation of anticancer therapy response. Nuclear imaging techniques may assist in the vivo assessment of DNA damage (doubleand single-strand brakes) as well as apoptosis intensity in tumor and normal tissues. [99mTc]- duramycin is the most commonly used tracer for imaging of apoptosis. Changes in tumor cell proliferation in response to anticancer therapy can be assessed by PET imaging with [18F]-FLT. Conclusion. Nuclear medicine offers a unique means to study cancer biology in vivo and to optimize cancer therapy.
1 November 2018 in Pharmaceutical Chemistry Journal
Neutron Capture Therapy (NCT) — highly selective method of binary radiotherapy of malignancies, which is based on physical phenomenon of thermal neutron radiation capture by atoms’ nuclei. Currently only 10B mediated NCT, known as boron neutron capture therapy (BNCT), is used in clinical practice. Boronophenylalanine — a modified amino acid is most widely used as 10B carrier. Despite of more than 70-years history of BCNT clinical application and promising results of curing patients with different tumors, this method of treatment is still under research and development. The most urgent issue is studying and prediction of radiation effects of healthy and tumor tissues after BNCT application. This task can be solved in experiments involving animals. The review contains results of BNCT studies both in laboratory animals with different tumor models and veterinary practice. Induced and transplanted models of central nervous system, oral cavity as well as subcutaneous and metastatic models are considered in the review. Obtained results of the studies show possible high antitumor efficacy of BPA mediated BNCT and fundamentally different mechanisms of BNCT effect on tumor and healthy tissues comparing to other known types of radiotherapy. Many issues still require addition research with modern methods of studies, such as in vivo preclinical imaging.
Background. For preclinical studies of radiopharmaceuticals there is a high need for development new methods of in vivo metastasis diagnosis in mice after tumor cells transplantation. The study was carried out to assess feasibility of lung metastasis diagnosis with magnetic resonance imaging (MRI) visualization in mice C57Bl6.The aim of this study was to assess feasibility of MRI for verification of distant metastases of the solid B16-F10 melanoma with validation by anatomic dissection.Methods. Metastatic lesions were caused by injection of B16-F10 murine melanoma cells into cavum medullare of the tibia. Imaging studies were performed on the 21th day after transplantation using 7T magnetic resonance tomograph, coronal and axial images were acquired. Validation of metastasis was made by anatomic dissection and histological examination.Results. MRI method enables visualization of lung nodules with diameter at least 0.8 mm, because smaller nodules cannot be distinguished from heartbeat artifacts. Histological examination revealed that macroscopic anatomic dissection can precisely detect subpleural lung nodules.Conclusion. This study demonstrated feasibility of in vivo lung metastasis verification with MRI method in mice: metastases comparable in diameter to the size of large bronchi can be detected by MRI as well as by ex vivo dissection. For centrally located lung metastasis MRI method is preferable because macroscopic dissection enables to visualize only nodules which are located subpleurally.