<p>A Chelate-Free Nano-Platform for Incorporation of Diagnostic and Therapeutic Isotopes</p>
Yaser H. GholamiLee JosephsonEman A. AkamPeter CaravanMoses Q. WilksXiang-Zuo PanRichard MaschmeyerAleksandra KolnickGeorges El FakhriMarc D. NormandinZdenka KuncicHushan Yuan
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Purpose: Using our chelate-free, heat-induced radiolabeling (HIR) method, we show that a wide range of metals, including those with radioactive isotopologues used for diagnostic imaging and radionuclide therapy, bind to the Feraheme (FH) nanoparticle (NP), a drug approved for the treatment of iron anemia. Material and methods: FH NPs were heated (120°C) with nonradioactive metals, the resulting metal-FH NPs were characterized by inductively coupled plasma mass spectrometry (ICP-MS), dynamic light scattering (DLS), and r 1 and r 2 relaxivities obtained by nuclear magnetic relaxation spectrometry (NMRS). In addition, the HIR method was performed with [ 90 Y]Y 3+ , [ 177 Lu]Lu 3+ , and [ 64 Cu]Cu 2+ , the latter with an HIR technique optimized for this isotope. Optimization included modifying reaction time, temperature, and vortex technique. Radiochemical yield (RCY) and purity (RCP) were measured using size exclusion chromatography (SEC) and thin-layer chromatography (TLC). Results: With ICP-MS, metals incorporated into FH at high efficiency were bismuth, indium, yttrium, lutetium, samarium, terbium and europium (> 75% @ 120 o C). Incorporation occurred with a small (less than 20%) but statistically significant increases in size and the r 2 relaxivity. An improved HIR technique (faster heating rate and improved vortexing) was developed specifically for copper and used with the HIR technique and [ 64 Cu]Cu 2+ . Using SEC and TLC analyses with [ 90 Y]Y 3+ , [ 177 Lu]Lu 3+ and [ 64 Cu]Cu 2+ , RCYs were greater than 85% and RCPs were greater than 95% in all cases. Conclusion: The chelate-free HIR technique for binding metals to FH NPs has been extended to a range of metals with radioisotopes used in therapeutic and diagnostic applications. Cations with f-orbital electrons, more empty d-orbitals, larger radii, and higher positive charges achieved higher values of RCY and RCP in the HIR reaction. The ability to use a simple heating step to bind a wide range of metals to the FH NP, a widely available approved drug, may allow this NP to become a platform for obtaining radiolabeled nanoparticles in many settings. Keywords: nanomedicine, radiolabeling, radionuclide therapy, HIR, FerahemeKeywords:
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Abstract ESR of Mo 3+ ions and NMR of 27 Al nuclei is investigated in mixed single crystals of yttrium‐lutetium‐aluminum garnets (Y 1 − x Lu x ) 3 Al 5 O 12 , where O ≦ x ≦ 1. Several new centres of Mo 3+ and 27 Al compared with Y 3 Al 5 O 12 and Lu 3 Al 5 O 12 single crystals are revealed associated with symmetry and crystalline field parameter changes at isomorphous substitution of Y 3+ ions in the rare‐earth sublattice of the garnet by those of Lu 3+ . Symmetry, nearest coordination, and parameters of spin‐Hamiltonians are estimated concerning all of Mo 3+ and 27 Al centres in (Y 1 − x Lu x ) 3 Al 5 O 12 , at x < 0.15.
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CALCULATION OF PRODUCTION OF GOLD-198, IRRIDIUM-192 AND LUTETIUM-177 BY NEUTRON ACTIVATION FOR RADIOACTIVE NANOPARTICLE. It was reported that nanoparticle was effective for cancer treatment by thermotherapy. It is also possible to kill cancer cell by radiation of radioisotope from nanoparticle. A study on production of radioactive nanoparticles by neutron activation has been carried out. Nanoparticles of gold, iridium and lutetium with diameter of 100 nm were studied. Calculations were carried out for irradiation at central irradiation position (CIP) of GA siwabessy reactor for 12 days. Calculation results showed that gold-198 with radioactivity of 0.378 Bq was produced in the gold nanoparticle. In the irridium nanoparticle, 192Irwith radioactivity of 0.179 Bq was produced. Radioisotope of 194Irwas also produced with radioactivity 0.337Bq at the end of irradiation in the iridium nanoparticle. The radioisotop decayed fast and became 0.000133Bq after 10 days. In the lutetium nanoparticle, I77Lu with radioactivity of 0.0884Bq was produced. In the lutetium nanoparticle, 176mLuand 177mLuwere also produced. Lutetium-176m decayed fast and I77Lu radioactivity was 0.0095% of the I77Lu radioactivity at the end of irradiation. During neutron irradiation, the nanoparticle was put in the quartz ampule and aluminum capsules. Radioisotopes with short half life were produced in the quartz and aluminum. Keywords: gold-198, iridium-l92, lutetium-l77, neutron activation 27
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