Neutron capture therapy (NCT) is a promising method of curing cancer, which uses stable isotopes with large thermal neutron capture cross section value (a) to provide selective damage of a tumor. Boron isotope 10 B (a = 3880 barn) is the most know and most widely used in NCT isotope. Gadolinium isotope 157Gd has even larger thermal neutron capture cross section value ( σ = 254 000 barn) than 10 B, but secondary radiation emitted by this isotope as the results of neutron capture nuclear reaction is absorbed by tumor tissues less effectively than for 10 B. The purpose of this research was to study gadolinium neutron capture therapy efficacy in curing spontaneous tumors. 13 dogs diagnosed with oral cavity spontaneous melanoma were studied. MRI contrast drug Dipentast® was used as a gadolinium containing substance. The drug was injected directly into the tumor immediately before neutron irradiation. The administered dose of the drug was 10 mg of gadolinium per 1 cm 3 of tumor. The irradiation was made with thermal neutron beam with neutron flux 7x10 8 n/cm 2 s and 3-6 cm diameter. The duration of irradiation was 70 minutes. As the results of the therapy complete tumor regression was achieved in 46 % of animals. Recurrence free period was 106.0±7.5 days for 66.7 % of dogs with complete tumor regression and more than 150 days for 16.7 %.

Targeted radioimmunotherapy is a promising approach to radiotherapy. Tumor-specific compounds were synthesized using monoclonal antibodies anti-ICO-25 (MUC1) and anti-ICO-80 (CD5) labeled with the therapeutic radioisotope 188Re. The specificity of the conjugates was demonstrated in vitro using SKOV-3 (ovary cancer) and Jurkat tumor cell lines (T-lymphoblastic lymphoma), which are known to have membrane surface receptors specific for the corresponding antibodies. Short-term survival tests revealed 90-93% death of tumor cells, indicating the proposed conjugates were promising for targeted delivery of diagnostic and therapeutic cancer drugs.

This paper analyses modern hi-tech methods of diagnosing health problems with the help of X-ray contrast agents used in combination with such technologies as magnetic resonance imaging, single-photon emission computer tomography, etc. The lack of Russian diagnostic drugs is the main hindrance to a wide clinical use of advanced medical diagnostic technologies. The article demonstrates the necessity of developing guidelines which would standardize the scope and nature of preclinical studies for all classes of X-ray contrast agents. The article suggests the main concepts that the guidelines should contain: the definition of the term «diagnostic drug»; the classification of diagnostic drugs by their chemical structure and/or pharmacological action; the required scope of obligatory and additional studies for new drugs and for new indications for already approved drugs; the objectives of experimental pharmacokinetic studies and acceptable methods of obtaining primary data; the list of methods to be used for electronic processing of primary data; evaluation of X-ray contrast agents safety (especially radiopharmaceuticals and PET radiopharmaceuticals), and the standard protocol of test results.

Contrast-enhanced radiotherapy (CERT) is a binary treatment modality in which the absorbed radiation dose is not only determined by the parameters of the external radiation source but also affected by the concentration of a dose-enhancing agent (DEA) in the studied object. In this work we assessed the distribution of the absorbed dose in a murine B16F10 melanoma injected with a single dose of an aqueous Bi-DTPA solution. The mice were exposed to a single fraction of X-ray irradiation for 28.5 min. In vivo measurements of DEA concentrations were done on a micro-CT scanner using the radiopacity values of malignant tissues from the obtained CT images. We found that the presence of DEA enhanced the absorbed dose more than twofold in 6% of the tumor volume; in 29% of the tumor volume the absorbed dose increased more than onefold. The tumor growth delay time calculated for our model was 0.76 days (we only accounted for the damage caused directly by radiation), whereas in our previous research study tumor growth delay was 10 days. This discrepancy may indicate that in the tumors exposed to contrast-enhanced radiotherapy growth delay results from both the damage directly caused by radiation and other antitumor mechanisms.

В фотон-захватной терапии (ФЗТ) величина поглощенной дозы определяется не только параметрами облучения, но и концентрацией дозоповышающего агента (ДПА) в облучаемом объекте. В данной работе было проведено расчетно- экспериментальное исследование распределения поглощенной дозы на опухолевой модели мышиной меланомы B16F10, после однократной интратуморальной инъекции висмута в качестве ДПА в форме водного раствора комплекса Bi-ДТПА. Оценку поглощенной дозы проводили для однофракционного рентгеновского облучения длительностью 28,5 мин. Количественное определение ДПА in vivo осуществляли при помощи микро-КТ, используя значения рентгеноплотности опухолевых тканей на полученных КТ-томограммах. В результате исследования установлено, что за счет присутствия ДПА в 6% объема опухоли поглощенная доза увеличивалась более чем в 2 раза и в 29% объема опухоли наблюдалось увеличение поглощенной дозы отличное от 1. Время задержки роста опухоли, рассчитанное для полученного дозо-объемного распределения с учетом только непосредственного радиационного поражения опухолевых клеток, составило 0,76 суток, тогда как в ранее проведенных экспериментальных исследованиях данная величина равнялась 10 суткам. Полученное несоответствие может указывать на то, что торможение роста опухоли при ФЗТ с интратуморальным введением ДПА достигается за счет не только непосредственного радиационного поражения опухоли, но и иных противоопухолевых механизмов.

This paper analyses modern hi-tech methods of diagnosing health problems with the help of X-ray contrast agents used in combination with such technologies as magnetic resonance imaging, single-photon emission computer tomography, etc. The lack of Russian diagnostic drugs is the main hindrance to a wide clinical use of advanced medical diagnostic technologies. The article demonstrates the necessity of developing guidelines which would standardize the scope and nature of preclinical studies for all classes of X-ray contrast agents. The article suggests the main concepts that the guidelines should contain: the definition of the term «diagnostic drug»; the classification of diagnostic drugs by their chemical structure and/or pharmacological action; the required scope of obligatory and additional studies for new drugs and for new indications for already approved drugs; the objectives of experimental pharmacokinetic studies and acceptable methods of obtaining primary data; the list of methods to be used for electronic processing of primary data; evaluation of X-ray contrast agents safety (especially radiopharmaceuticals and PET radiopharmaceuticals), and the standard protocol of test results.

The efficacy of photon capture therapy (PCT) is to a significant extent determined by the properties of the formulation containing the element efficiently absorbing external X-irradiation and operating as a dose-enhancing agent (DEA). We report here a comparison of the efficacies of bismuth and gadolinium as DEA in PCT technologies with X-irradiation at 110 kV for the treatment of superficial tumors. Bismuth and gadolinium are comparable in that they are available as the same chemical form – a complex with diethylenetriaminepentaacetic acid, for which the physicochemical properties are similar for both elements. Studies were performed on mice with transplanted B16F10 melanoma as a tumor model. Both DEAwere given by the intratumor route at the same dose of 5 mg of DEAper animal. Irradiation was with an x-ray apparatus with a tension of 110 kV using a dose of 20 Gy. The results showed significantly greater antitumor efficacy for PCT with both gadolinium and bismuth than with short-focus radiotherapy. In terms of the log dead cells (lgN), there was an increase in lgN from 0.78 for short-focus irradiation to 2.5 for PCT using gadolinium or bismuth, with identical dose exposure. There were no significant differences in the antitumor efficacies of PCT with bismuth and gadolinium for x-ray irradiation at 110 kV.

Asynthetic scheme for a transport platform for the creation of new diagnostic and therapeutic antitumor drugs that was based on a dendrimer with a core of pentaerythritol tetraglycidyl ether (TGEPE) and dendra with diallylamine was developed. The transport platform was promising for designing targeted antitumor agents for magnetic resonance tomography and nuclear medicine.

The review is devoted to the problems of the development of binary technologies of radiation therapy neutron and photon-capture therapy of malignant neoplasms. These technologies are based on the principle of "biological" targeting: irradiation of a tumor with pre-delivered special preparations increasing energy release and the relative biological efficiency of primary radiation. The basis of methods, characteristics of sources of external irradiation and used preparations, and stages of development of technologies are described. The development and implementation of binary technologies attract a great number of researchers but are restrained by the shortage of operating sources of epithermal neutrons (reactors, neutron generators based on accelerators) and the lack of accurate radiation dosimetry planning systems that takes into account the dynamics and accumulation of drugs in tumors.

Contrast-enhanced radiotherapy (CERT) is a type of radiation therapy used to enhance the radiation dose absorbed by the tumor while sparing surrounding healthy tissues. The present study aims to assess feasibility of using 6 MV photons to increase radiation absorption in CERT. The dose absorbed by iodinated water was directly measured by ferrosulphate dosimetry. Concentrations of iodine (a dose-enhancing agent) ranged from 2.5 to 50 mg/ml. Solutions were exposed to 5 Gy radiation generated by the clinical linear accelerator SL75-5MT (Russia). The radiation dose applied did not account for increased absorbance due to the presence of iodine atoms. No reliable increase in the absorbed dose was observed for iodine concentrations ranging from 2.5 to 20 mg/ml. For 50 mg/ml concentrations the absorbed dose increased by 13% +/- 5 % (p < 0.05). Normally, dose-enhancing concentrations observed in CERT studies range from 2.5 to 15 mg/ml, therefore, as demonstrated by our findings, employing 6 MV photon energy spectra in order to reach a therapeutically significant effect is unreasonable.

Purpose or Objective: To investigate the association between external beam radiotherapy (EBRT) and pleural and peritoneal mesothelioma among long-term (>5 years) solid cancer survivors. Material and Methods:We analysed data from the US Surveillance, Epidemiology, and End Results (SEER) program .We fitted survival models adjusted by age, gender, race, year, surgery, and relative risk of primary mesothelioma in the county of residence (proxy for individual asbestos exposure).We estimated hazard ratios [HR] with reference to non-irradiated patients.We distinguished between scattered and direct irradiation to study the doseresponse. Results:We observed 300 mesotheliomas (264 pleural; 32 peritoneal; 4 others) among 913,873 patients.EBRT increased the risk of mesothelioma (any site; HR 1.36, 95%CI 1.05-1.76).We observed an increased risk of pleural mesothelioma (HR for EBRT 1.35, 95%CI 1.02-1.78),but we did not find signs of a dose-response relationship (HR for scattered irradiation 1.35; HR for direct irradiation 1.36).On the opposite, only direct peritoneal irradiation was associated with peritoneal mesothelioma (HR 2.13,, particularly for latencies ≥10 years (HR 3.19,.A competing risks analysis revealed that the clinical impact of radiationinduced mesothelioma was limited by the high frequency of competing events.The cumulative incidence function of mesothelioma after 40 years of observation was very low (non-irradiated patients: 0.00031, irradiated patients: 0.00056). Conclusion:EBRT is a determinant of mesothelioma.Longer latency periods are associated with higher risks, while the dose-response seems non-linear.The clinical impact of mesothelioma after EBRT for primary solid cancers is very limited.

To improve the safety of Gd3+-based contrast agents (GBCA) in clinical practice, it is recommended to use the most stable substances and to consider conditions determining their stability. The aim of this study was to compare the stability of GBCAs for magnetic resonance imaging in the presence of zinc and calcium ions and polyvinylpyrrolidone (PVP) in water, phosphate buffer solution and blood serum using proton NMR relaxometry. The study demonstrated that macrocyclic gadobutrol is more stable than all linear contrast agents. The addition of PVP (10 mg/ml) improved the stability of linear GBCAs in phosphate buffer solution and blood serum. Calcium ions have a much weaker destabilizing effect on GBCAs than zinc ions.

Binary radiotherapy (BRT) is a type of radiation therapy that employs special drugs to direct ionizing radiation to a target. As a rule, the drug has no significant biological activity of its own. BRT causes damage due to interaction of secondary ionizing radiation with biological tissues. The special drug that accumulates selectively in a tumor contains chemical elements that absorb external ionizing radiation considerably more efficiently than the chemical elements in living tissues. The absorbed dose can increase from several percent up to five times as a result of the selective interaction of the external radiation with such drugs in tumors. Currently, two types of BRT exist, i.e., neutron-capture therapy (NCT), which uses neutron beams, and photo-capture therapy (PCT), which uses x-rays. NCT potentially has greater therapeutic efficacy than PCT. However, PCT equipment is less expensive and can be housed in existing clinical establishments. Numerous studies of BRT efficacy from many countries of the world indicate that this technology is potentially efficacious for treating malignancies. Introduction of BRT into clinical practice would enhance considerably the antitumor efficacy of radiotherapy and decrease the number of irradiations to a single one. The capability of BRT can be fully unleashed only by developing specialized drugs that satisfy the BRT requirements.

In vivo quantitative determination of high-Z elements such as iodine gadolinium, gold, etc. is an important issue for contrast enhanced radiotherapy (CERT) that aggravates its clinical implementation. X-ray computed tomography (CT) could be a reliable, convenient and universal method for this task. The aim of this study was to demonstrate the feasibility of iodine quantification with CT in a tissue equivalent phantom, meeting the demands for CERT. The results show a linear relationship between iodine concentration and radiopacity on tomographic images expressed in Hounsfield units (HU) over an iodine concentration range of 0.5-50 mg/ml. Furthermore, iodine quantification with CT proofed to be suitable for CERT since the deviation between CTderived and actual iodine concentration does not exceed 5 % in the concentration range of 10-50 mg/ml. More significant deviations were observed for concentrations below 5 mg/ml with up to 80 %, which is still acceptable for CERT since the corresponding error for the absorbed dose in that range is less than 2.8 %. X-ray beam hardening within the tissue equivalent object does not significantly influence the accuracy of iodine quantification. The placement of iodine water solutions at the surface or in the centre of a visualized object during iodine quantification leads to a less than 2 % change in the determined iodine concentration.

Contrast-enhanced magnetic resonance imaging has become a routine diagnostic procedure. One of the most common contrast agents used for MRI is gadopentetic acid (Gd-DTPA, marketed as Magnevist). In this work, we studied the relaxivity of Gd-DTPA covalently bonded to beta-cyclodextrin and compared enhancement properties of this compound and Magnevist. Our work demonstrated high relaxivity of Gd-DTPA complex containing 80 % of Gd-DTPA-modified beta-cyclodextrin mono-derivative, 10 % of Gd-DTPA-modified beta-cyclodextrin di-derivative and 10 % of Gd-DTPA-modified beta-cyclodextrin tri-derivative. Gd-DTPA residues were linked to beta-cyclodextrin by an ester bond, in which a COOH group belongs to DTPA and OH is a beta-cyclodextrin surface hydroxyl group. It was proved experimentally that the studied compound is not toxic in concentrations necessary for diagnostic procedures. Compared to Magnevist, it can provide similar enhancement when used in just half of the equivalent amount.