Applied Radiation and Isotopes 161 (2020) 109161 Available online 2 April 2020 0969-8043/© 2020 Elsevier Ltd. All rights reserved. A kit based methodology for convenient formulation of 166 Ho-Chitosan complex for treatment of liver cancer Sharad Lohar a , Sachin Jadhav a , Rubel Chakravarty a, c, * , Sudipta Chakraborty a, c , Haladhar Dev Sarma b , Ashutosh Dash a, c a Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India b Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India c Homi Bhabha National Institute, Anushaktinagar, Mumbai, 400 094, India A R T I C L E INFO Keywords: 166 Ho Chitosan Liver cancer Radiopharmaceutical Trans-arterial radionuclide therapy Two-vial kit ABSTRACT The effectiveness of 166 Ho-chitosan complex as a radiopharmaceutical for trans-arterial radiation therapy of liver cancer has been established in clinical trials. We have developed a simple kit-bade strategy for convenient formulation of therapeutically relevant doses of 166 Ho-chitosan complex in a hospital radiopharmacy in order to facilitate its widespread utilization. Quality control studies established the suitability of the radiopharmaceutical formulated using the developed strategy for in vivo administration. Biodistribution studies in normal Wistar rats showed excellent retention of the radiopharmaceutical in the liver, thus, paving the way towards utility of this approach in clinical context. 1. Introduction Despite high incidences of liver cancer worldwide, treatment options for the patients are still limited and therefore, this disease has become a major cause of mortality (Daher et al., 2018). In addition to the primary liver cancer, a large number of patients with colorectal cancer eventu- ally develop metastatic lesions in the liver (Fujino and Miyoshi, 2019; Nace et al., 2011). Although, hepatic resection is the most commonly used treatment option in such ailments, several patients are ineligible for this therapeutic modality because of the complicated features of their metastatic lesions (size, number and location) and the presence of extra-hepatic diseases (Daher et al., 2018). The other treatment options, including, percutaneous ethanol injection therapy, hepatic cryotherapy, radiofrequency ablation and laser photocoagulation have shown only marginal improvement in patient survival (Salhab and Canelo, 2011). Trans-arterial radiation therapy using suitable β - emitting radionuclides is a viable option for improving survival rate of liver cancer patients and has emerged as a promising clinical alternative towards liver cancer management (Andrews et al., 1994; Bouvry et al., 2018; Prince et al., 2018). Generally, in trans-arterial radiation therapy, radioactive micro- spheres with diameter in the range of 20–50 μm are administered through the hepatic artery and placed in the direct vicinity of the liver tumors in order to deliver high radiation doses directly to the malignant cells, while leaving the healthy tissues unaffected (Bouvry et al., 2018). Several generations of radioactive microspheres incorporating thera- peutic radionuclides, mainly 90 Y, have been developed over the last few decades and are available commercially, albeit, at an exorbitantly high cost (Bouvry et al., 2018). In selected liver cancer patients, treatment with radioactive microspheres have demonstrated promising clinical outcome (Andrews et al., 1994; Bouvry et al., 2018; Prince et al., 2018). However, non-uniform distribution of the radioactive microspheres in the cancerous lesions leading to sub-optimal therapeutic effcacy in certain cases and diffcult catheterization for administration of the mi- crospheres are some of the issues which have not yet been fully resolved (Vesselle et al., 2015). From this perspective, the use of radio- embolization agents based on radiolabeled viscous liquid holds promise in liver cancer therapy. In the past, formulation of a wide variety of radiolabeled viscous liquids, such as, 131 I-lipiodol (Dumortier et al., 2014; Mukherjee et al., 2017; Wu et al., 2016), 188 Re-lipiodol (Banka et al., 2015; De Ruyck et al., 2004; Delaunay et al., 2019; Esquinas et al., 2018), 66 Ga-chitosan complex (Pourjavadi et al., 2011), 153 Sm-chitosan complex (Shin et al., 2001), 166 Ho-chitosan complex (Seong et al., 2005; Suzuki et al., 1998), 131 I-chitosan hydrogel (Hwang et al., 2017), etc. have been reported. These agents have their own merits and limitations which determine * Corresponding author. Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India. E-mail addresses: rubelc@barc.gov.in, rubelchakravarty@gmail.com (R. Chakravarty). Contents lists available at ScienceDirect Applied Radiation and Isotopes journal homepage: http://www.elsevier.com/locate/apradiso https://doi.org/10.1016/j.apradiso.2020.109161 Received 20 June 2019; Received in revised form 26 February 2020; Accepted 27 March 2020