Antitumor efficacy of extracellular complexes with gadolinium in Binary Radiotherapy A.A. Lipengolts a,b,c,n , A.A. Cherepanov a,b,c , V.N. Kulakov b , E.Yu. Grigorieva a , I.N. Sheino b , V.A. Klimanov c a Blokhin Russian Cancer Scientific Centre, Kashirskoe sh. 24, Moscow, Russian Federation b Burnasyan Federal Medical Biophysical Centre, Zhivopisnaya 46, Moscow, Russian Federation c National Research Nuclear University “MEPhI”, Kashirskoe sh. 31, Moscow, Russian Federation HIGHLIGHTS  A new approach of using extracellular drugs in Binary Radiotherapy was proposed.  Vascularization of three different transplanted murine tumors was studied.  Significant efficacy of CERT with Gd-DTPA in curing adenocarcinoma Ca755 was shown. article info Article history: Received 30 January 2015 Received in revised form 10 July 2015 Accepted 27 July 2015 Available online 29 July 2015 Keywords: Binary Radiotherapy Gadolinium X-rays Adenocarcinoma Ca755 Transplanted tumors Mice Animal study abstract In this report the efficacy of extracellular pharmaceutical Gd-DTPA in Binary Radiotherapy was studied. The study was carried out in mice bearing transplantable adenocarcinoma Ca755 using X-ray based contrast enhanced radiotherapy as a practical implementation of Binary Radiotherapy. It was shown that intravenous administration of 0.3 ml of 0.5 M water solution of Gd-DTPA followed by X-irradiation at a dose of 10 Gy provides T/C% ¼10 73% and leads to complete tumor regression in 25% of mice. & 2015 Elsevier Ltd. All rights reserved. 1. Introduction Binary Radiotherapy is a developing method of radiotherapy which uses special pharmaceuticals (let us call them BRT-drugs) to form absorbed dose field of desirable shape (Kulakov et al., 2013). Formation of absorbed dose field is caused by preferential inter- action of external radiation with specific element (absorbing ele- ment) contained in a BRT-drug (Sheino, 2006). For example, thermal neutrons are more likely to interact with Gd and 10 B than with elements comprising soft tissues (H, N, C, O etc.), while X-rays with Gd, Au, Pt and other heavy elements as the result of photoabsorption. (Butterworth et al., 2012). Thus, saturation of a tumor with a pharmaceutical, which contains such absorbing elements and irradiation of it with certain type of radiation (neutrons or X-rays) leads to significant increase of absorbed dose in a tumor region only (Verhaegen et al., 2005; Robar et al., 2002). A dose increase is proportional to the concentration of an ab- sorbing element. Practical implementations of this approach are Neutron Capture Therapy (NCT), utilizing thermal neutrons and 10 B or Gd as the target element, and Contrast Enhanced Radiotherapy (CERT)–utilizing X-rays and elements with Z 452 (I, Gd, Au etc.). The efficacy of Binary Radiotherapy (both NCT and CERT) is highly dependent on the ratio of particular BRT-drug concentration in the tumor and the surrounding normal tissues (T/N ratio). Binary Radiotherapy has already been shown to be an effective tumor treating modality with intratumoral administration of iodine and Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/apradiso Applied Radiation and Isotopes http://dx.doi.org/10.1016/j.apradiso.2015.07.051 0969-8043/& 2015 Elsevier Ltd. All rights reserved. n Corresponding author at: Blokhin Russian Cancer Scientific Centre, Kashirskoe sh. 24, Moscow, Russian Federation. E-mail address: lipengolts@mail.ru (A.A. Lipengolts). Applied Radiation and Isotopes 106 (2015) 233–236