A Freeze-Dried Kit for the Preparation of 188 Re-HEDP for Bone Pain Palliation: Preparation and Preliminary Clinical Evaluation Madhava B. Mallia, 1 Ajit Sugunan Shinto, 2 Mythili Kameswaran, 3 Koramadai Karuppusamy Kamaleshwaran, 2 Radhakrishnan Kalarikal, 2 K.K. Aswathy, 2 and Sharmila Banerjee 1 Abstract 188 Re-HEDP is an established radiopharmaceutical used for pain palliation in patients with osseous metastasis. Considering commercial availability of 188 W/ 188 Re generator, the accessibility to a lyophilized kit would make preparation of this radiopharmaceutical feasible at the hospital radiopharmacy having access to a generator. A protocol for the preparation of a single-vial lyophilized hydroxyethane 1,1-diphosphonic acid (HEDP) kit was developed and its consistency was checked by preparing six batches. Each sterile lyophilized kit prepared as per the protocol contained 9 mg of HEDP, 3 mg of gentisic acid, and 4 mg of SnCl 2 .2H 2 O. Randomly selected kits from all six batches were subjected to thorough quality control tests that were passed by all batches. 188 Re- HEDP could be prepared by addition of 1 mL of freshly eluted Na 188 ReO 4 (up to 3700 MBq) containing 1 lmol of carrier ReO 4 - (perrhenate) and heating at 100°C for 15 minutes. 188 Re-HEDP with >95% radiochemical purity could be consistently prepared using the lyophilized kits. Sterile 188 Re-HEDP prepared using the ly- ophilized kit was evaluated in patients with osseous metastasis. Post-therapy images of the patient were compared with 99m Tc-MDP bone scan and found to be satisfactory. The bone-to-background as well as tumor- to-normal bone uptake ratio was found to be significant. All patients who received therapy reported significant pain relief within a week to 10 days post-administration of 188 Re-HEDP. Key words: bone pain palliation, HEDP, lyophilized kit, osseous metastasis, Rhenium-188 Introduction B one metastasis is common in patients with cancers of prostate, breast, lung, bladder, and thyroid. Problems associated with bone metastasis include severe pain, patho- logical fracture, spinal cord compression etc., which can compromise the quality of life of the patient by affecting mobility and sleep. Clinical management of pain itself can significantly improve the quality of life of the patient. To achieve this, a treatment modality that can be repeated and well tolerated by the patient is necessary. At present, avail- able options are the use of conventional analgesics, external beam radiation therapy, and radionuclidic therapy. 1,2 Radionuclidic therapy is one of the modalities widely being practiced for bone pain palliation. This involves se- lective delivery of radiation dose to the affected bone lesions, which are responsible for pain to the patient. Radio- pharmaceuticals for bone pain palliation have a long history. For example, 32 P (as orthophosphate) was used as early as 1932. 3 Strontium-89 chloride (MetastronÔ) is an FDA- approved radiopharmaceutical for the treatment of bone pain. 4,5 Thereafter, several other radiopharmaceuticals, such as 153 Sm- EDTMP (Quadramet Ò ; EDTMP—ethylenediamine tetra- methylene phosphonic acid), 6 186 Re-HEDP (hydroxyethane 1, 1-diphosphonic acid), 7 and 188 Re-HEDP 8 , have been clinically used for bone pain palliation. 177 Lu-EDTMP is the latest entry to the list of clinically useful bone pain palliating agents. 9 Guerra Liberal el al. recently reviewed therapeutic radiophar- maceuticals for bone pain palliation and provided a perspective beyond 89 Sr and 153 Sm. 10 1 Radiopharmaceuticals Chemistry Section, Radiochemistry & Isotope Group, Bhabha Atomic Research Centre, Mumbai, India. 2 Department of Nuclear Medicine and PET/CT, Kovai Medical Center and Hospital Limited, Coimbatore, India. 3 Isotope Production and Applications Division, Radiochemistry & Isotope Group, Bhabha Atomic Research Centre, Mumbai, India. Address correspondence to: Madhava B. Mallia; Radiochemistry & Isotope Group, Radiopharmaceuticals Chemistry Section, Bhabha Atomic Research Centre; I-61, RPhCS, Isotope wing, RLG Building, Mumbai 400 085, India E-mail: mallia@barc.gov.in CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS Volume 31, Number 4, 2016 ª Mary Ann Liebert, Inc. DOI: 10.1089/cbr.2016.2030 139 FOR PERSONAL USE ONLY NOT INTENDED FOR DISTRIBUTION OR REPRODUCTION