A Facile Strategy for Preparation of Yttrium-90 Therapeutic Sources for Radionuclide Therapy.

Background: Mold brachytherapy using high-energy ß--emitting radioisotopes is a promising treatment modality for skin cancers and keloids. Simple methodologies for consistent and stable incorporation of radionuclides into the matrix are desired for preparation of therapeutic sources. Methods: The authors report a facile strategy for the stable incorporation of Yttrium-90 (90Y) into amidoxime-functionalized polyacrylonitrile-polyvinylidene fluoride (PAN-PVDF) membranes. The strategy consisted of surface modification of PAN-PVDF membranes by reaction with hydroxylamine, characterization of the functionalized membranes, and optimization of experimental variables for maximum loading of 90Y onto the membranes. Quality control tests essential for confirming the suitability of the 90Y therapeutic sources for human application, such as uniformity of activity distribution, absence of leaching of activity, and estimation of surface contamination, were performed. Theoretical calculations to estimate the dose imparted by the 90Y therapeutic sources at varying depths of tissue were also carried out to predict the possible therapeutic outcome of treatment. Results: A facile method for large-scale preparation of 90Y-based mold brachytherapy sources could be established. Conclusions: The source fabrication methodology standardized in this work could be tailored for fabrication of custom-made 90Y sources for individualized treatment of superficial tumors, Bowen's disease, and keloids.

Synthesis and Preliminary Biological Evaluation of 177Lu-Labeled Polyhydroxamic Acid Microparticles Toward Therapy of Hepatocellular Carcinoma.

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 177Lu-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 177Lu on PHA microparticles. Stability of 177Lu-PHA microparticles was tested in the presence of competing Fe(III) ions in solution. In vitro stability of 177Lu-PHA microparticles was evaluated in 0.05 M sodium phosphate solution (pH 7.5), saline, and serum. Bioevaluation studies were performed in normal Wistar rats by intrahepatic artery injection of the 177Lu-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 µm, suitable for TARE. Under the optimized conditions, >99% loading of 177Lu on PHA microparticles could be achieved. Even in the presence of high concentration of Fe(III) ions, 177Lu binding to PHA microparticles was stable. 177Lu-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 177Lu-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 177Lu for treatment of HCC.

Preparation of Radioactive Skin Patches Using Polyhydroxamic Acid-Grafted Cellulose Films Toward Applications in Treatment of Superficial Tumors.

The primary objective of this investigation is the development of a strategy for the synthesis of polyhydroxamic acid (PHA)-grafted cellulose film, its characterization, and evaluation of its usefulness for the preparation of 177Lu skin patches for superficial brachytherapy applications. PHA-grafted cellulose films were synthesized and characterized by Fourier transformed infrared spectrometer analysis and visual color test with Fe(III) solution. Uptake of 177Lu on the PHA-grafted cellulose was investigated by varying the experimental conditions such as the pH of feed solution, amount of nonradioactive Lu carrier, time, and temperature of the reaction. Under the optimized conditions, >95% loading of 177Lu on the PHA-cellulose film could be achieved. Autoradiography studies of 177Lu-PHA-cellulose film confirmed the uniform distribution of 177Lu on the surface. Energy dispersive X-ray analysis of nonradioactive Lu-PHA-cellulose film confirmed the loading of Lu on PHA-cellulose film. The utility of PHA-functionalized cellulose films for the fabrication of radioactive sources for superficial brachytherapy applications could be successfully demonstrated.