Bio-data of

Novel Tc-99m radiopharmaceuticals

The notable achievements include radiolabeling promising agents like Diltiazem, Photosan-3, Acetylated LDL, Glucaric Acid, anti-CEA monoclonal antibody, Polyethylene Glycol (PEG), Tetraethylenepentaamine-Folate and Chitosan with Tc-99m and evaluation of their utility as radiodiagnostic agents in various experimental models of diseases.

Specific radiopharmaceuticals were developed based on folate, CCK & C-substituted bifunctional Salen derivatives for radiodiagnosis and therapy, and peptide / non-peptdic system for imaging nasopharyngeal tumor and for detecting primary or metastatic medullary thyroid cancer.
Humanized monoclonal antibody h-R3 was conjugated to new generation bifunctional macrocyclic DOTA-based chelating agents and labeled with diagnostic and therapeutic radionuclide for targeted imaging and therapy. In addition, developed and evaluated Sodium alginate nanospheres for bone marrow scintigraphy, Sulphur nano-colloids, Ultrafine modified Chitosan nanoparticles for drug delivery.

Novel bifunctional chelating agents based on macrocyclic framework were synthesized namely: 6-(4-isothiocyanatobenzyl)-5, 7-dioxo -1, 11 – (carboxymethyl) – 1, 4, 8, 11 – tetraazacyclotridecane and DOTA-Ph-Al was synthesized and labeled with Tc-99m and Y-90 for therapeutic application. The work has been highlighted in the front cover page of the Cancer Biology & Therapy (August 2005) as a paper entitled, ‘Radiolabeling and Biological Evaluation of DOTA-Ph-A1 Derivative Conjugated to anti-EGFR antibody ior egf/r3 for Targeted Tumor Imaging and Therapy’

Our paper entitled ‘Formulation of lyophilized cold kit for instant preparation of Tc-99m-glucarate and its scintigraphic evaluation in experimental models of infarction’, published in the Indian Journal of Pharmacology was selected for ‘Jaipur Award’ (2004) of Indian Pharmacological Society.

2. Ready-to-use Cold radiopharmaceutical Kits

An important factor in radiopharmaceutical dispensing has been the introduction of ‘ready-to-use kits’ which provide individual/multiple doses and can be reconstituted by addition of radionuclide at the time of intended use. Chemical reagents are prepared in a sterile environment using apyrogenic raw materials and dispensed into single/multiple unit dose containers. The preparation of individual doses can be carried out rapidly and safely when required with minimal manipulation.

Multicentric clinical trials of ‘Diagnobact’ & ‘Diagnomammo’ cold kits were started. A single vial cold kit of Ciprofloxacin (‘Diagnobac’”) was developed for bacterial infection imaging. Body’s immunity is compromised after radiation exposure, leading to proneness to microbial infections. Indigenously prepared Diagnobact kit on addition of Tc-99m pertechnetate, has been shown to possess excellent in vitro and in vivo labeling efficiency. Studies in animal model of infection followed by multicentric evaluation in human volunteers have confirmed that Tc-99m-Ciprofloxacin is a specific bacterial infection imaging agent. After obtaining DCGI permission, a case was submitted to Radiopharmaceutical Committee of BARC for permission to market it. On September 15, 2006 - BRIT has signed an MoU for production and marketing a diagnobact cold kit developed by INMAS. Dr. R.P. Triapthi, Director INMAS, and Dr. A.K. Kohli, Chief Executive, BRIT signed the MoU in presence of Maj Gen Umang Kapoor, the then Director, C-TECH, DRDO.

3. Development of novel Drug Delivery Systems and application of pharmacoscintigraphic technique for their preclinical evaluation

Developed and applied pharmacoscintigraphic technique for evaluation of formulations based on novel drug delivery systems (Conventional and Stealth Liposome formulations for anticancer drug delivery, Ocular drug delivery systems, Sodium alginate nanospheres for Bone marrow scintigraphy, Sulphur nano-colloids, Ultrafine modified Chitosan nanoparticles hydrodynamically balanced system, gastroretentive floating drug formulation, tripalmitin/Solid Lipid glyceride/ Poly(butyl cyanoacrylate) / PLGA / PCL nanoparticles, Polysorbate 80 coated Chitosan Nanoparticles, Polysorbate 20 micelles, Carbohydrate coated poly(propylene imine) dendrimers, Galactosylated Liposomes, Chitosan/ Albumin microspheres, and Microemulsions) in experimental models of disease. Above studies involving radioactive tagging, quality control and pharmacokinetic studies were carried out in active collaboration with Prof. R.S.R. Murthy & Prof. A. Misra of MS Univ of Baroda, Prof. N.K. Jain of Sagar University, Dr. Alka Ahuja and Dr. Javed Ali of Jamia Hamdard, Prof. Ranendra N. Saha of Birla Institute of Technology and Science, Pilani and Prof. AN Maitra of University of Delhi.

Two research scholars were awarded Ph.D. degrees in Chemistry discipline (Titles of Thesis: Investigations on Chitosan nanoparticles as potential drug delivery carriers; Studies on the trafficking of smart nanoparticles across blood-brain barriers) in the year 2004 and 2006 respectively from University of Delhi while working in the above programme.
My views on Nanotechnology for Drug Delivery have appeared in a NISCAIR publication entitled, ‘Health Technology as fulcrum of development for the Nation: The road ahead’ (pp 214-218, 2005). One of our published work about the nanoparticle distribution to tumors after various routes of administration has been identified and described in the "Nanotech News" of the National Cancer Institute of National Institute of Health, USA (http://nano.cancer.gov/news_center/nanotech_news_2005-06-27d.asp.).
American Association of Pharmaceutical Scientists (AAPS) has conferred 2008 AAPS Outstanding Manuscript Award in PharmSciTech on the manuscript entitled "Preliminary Brain Targeting Studies on Intranasal Mucoadhesive Microemulsions of Sumatriptan" published in the AAPS PharmSciTech 7(1), Article 8. (http://www.aapspharmscitech.org)

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