Synthesis and Preliminary Biological Evaluation of 177 Lu-Labeled Polyhydroxamic Acid Microparticles Toward Therapy of Hepatocellular Carcinoma Usha Pandey, 1,2 Suresh Subramanian, 1,2 Samina Shaikh, 2,3 Naresh Gamre, 1 Sanjukta Kumar, 2,3 and Ashutosh Dash 1,2 Abstract Background: Transarterial radioembolization (TARE) represents an effective targeted therapeutic option for hepatocellular carcinoma (HCC), a cancer with high mortality and poor prognosis. The aim of this study was the preparation and preliminary biological evaluation of 177 Lu-labeled polyhydroxamic acid (PHA) microparticles toward possible use in the therapy of HCC. Materials and Methods: PHA microparticles were synthesized starting from polyacrylamide. They were characterized by Fourier-transform infrared spectroscopy (FT-IR), visual color test, and laser diffraction particle size analysis. Experimental variables such as reaction pH, amount of PHA microparticles, carrier Lu content, and incubation time were optimized for maximum uptake of 177 Lu on PHA microparticles. Stability of 177 Lu– PHA microparticles was tested in the presence of competing Fe(III) ions in solution. In vitro stability of 177 Lu– PHA microparticles was evaluated in 0.05 M sodium phosphate solution (pH 7.5), saline, and serum. Bioe- valuation studies were performed in normal Wistar rats by intrahepatic artery injection of the 177 Lu–PHA microparticles. Results: Successful synthesis of PHA microparticles could be confirmed from the results of FT-IR analysis and visual color test. Laser diffraction-based particle size analysis confirmed median particle size to be 54 lm, suitable for TARE. Under the optimized conditions, >99% loading of 177 Lu on PHA microparticles could be achieved. Even in the presence of high concentration of Fe(III) ions, 177 Lu binding to PHA microparticles was stable. 177 Lu–PHA microparticles exhibited excellent in vitro stability in sodium phosphate solution, saline, and serum up to 5 d at 37°C. In the bioevaluation studies performed in normal Wistar rats, 92.8% – 3.1% of 177 Lu– PHA microparticles were retained in the liver at 96 h postinjection without any significant leakage to other organs. Conclusion: This preliminary study demonstrates the potential of synthesized PHA microparticles as carriers of therapeutic radioisotopes such as 177 Lu for treatment of HCC. Keywords: hepatocellular carcinoma, transarterial radioembolization, polyhydroxamic acid microparticles, 177 Lu, 177 Lu–PHA Introduction H epatocellular carcinoma (HCC) has emerged as one of the most common causes of cancer-related mortality globally, and its incidence is expected to increase in the coming decades. 1,2 Delayed manifestation of clinical symp- toms and absence of dedicated screening programs for spe- cific markers in underprivileged countries mean that majority of the patients are at advanced stages of the disease at the time of diagnosis, rendering them unsuitable for resective 1 Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India. 2 Homi Bhabha National Institute, Mumbai, India. 3 Analytical Chemistry Division, Bhabha Atomic Research Centre, Mumbai, India. Address correspondence to: Usha Pandey; Radiopharmaceuticals Division; Bhabha Atomic Research Centre; Trombay, Mumbai 400 085, India E-mail: ushap@barc.gov.in CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS Volume 34, Number 5, 2019 ª Mary Ann Liebert, Inc. DOI: 10.1089/cbr.2018.2747 306 Downloaded by 54.162.69.248 from www.liebertpub.com at 07/02/20. For personal use only.