Nanotargeted Radionuclides for Cancer Nuclear Imaging and Internal Radiotherapy

Current progress in nanomedicine has exploited the possibility of designing tumor-targeted nanocarriers being able to deliver radionuclide payloads in a site or molecular selective manner to improve the efficacy and safety of cancer imaging and therapy. Radionuclides of auger electron-, α-, β-, and γ-radiation emitters have been surface-bioconjugated or after-loaded in nanoparticles to improve the efficacy and reduce the toxicity of cancer imaging and therapy in preclinical and clinical studies. This article provides a brief overview of current status of applications, advantages, problems, up-to-date research and development, and future prospects of nanotargeted radionuclides in cancer nuclear imaging and radiotherapy. Passive and active nanotargeting delivery of radionuclides with illustrating examples for tumor imaging and therapy are reviewed and summarized. Research on combing different modes of selective delivery of radionuclides through nanocarriers targeted delivery for tumor imaging and therapy offers the new possibility of large increases in cancer diagnostic efficacy and therapeutic index. However, further efforts and challenges in preclinical and clinical efficacy and toxicity studies are required to translate those advanced technologies to the clinical applications for cancer patients

An in situ study on the coalescence of monolayer-protected Au-Ag nanoparticle deposits upon heating

The structural evolution of thiolate-protected nanoparticles of gold, silver, and their alloys with various Au/Ag ratios (3:1, 1:1, and 1:3) upon heating was investigated by means of in situ synchrotron radiation X-ray diffraction. The relationships between the coalescence and composition of nanoparticles, as well as the surfactant reactions, were clarified. Experimental results show that there existed a critical temperature ranging from 120°C to 164°C, above which the tiny broad X-ray diffraction peaks became sharp and strong due to particle coalescence. The coalescence temperatures for alloy nanoparticle deposits were clearly lower than those for pure metals, which can be ascribed to the rivalry between the thermodynamic effect due to alloying and the interactions between surface-assembled layers and the surface atoms of the nanoparticles. The strong affinity of thiolates to Ag and thus complex interactions give rise to a greater energy barrier for the coalescence of nanoparticles into the bulk and subsequent high coalescence temperature. The influences of particle coalescence on the optical and electrical properties of the nanoparticle deposits were also explored

Biodistribution and pharmacokinetics of 188Re-liposomes and their comparative therapeutic efficacy with 5-fluorouracil in C26 colonic peritoneal carcinomatosis mice

Chia-Che Tsai1, Chih-Hsien Chang1, Liang-Cheng Chen1, Ya-Jen Chang1, Keng-Li Lan2, Yu-Hsien Wu1, Chin-Wei Hsu1, I-Hsiang Liu1, Chung-Li Ho1, Wan-Chi Lee1, Hsiao-Chiang Ni1, Tsui-Jung Chang1, Gann Ting3, Te-Wei Lee11Institute of Nuclear Energy Research, Taoyuan, 2Cancer Center, Taipei Veterans General Hospital, Taipei, 3National Health Research Institutes, Taipei, Taiwan, ROCBackground: Nanoliposomes are designed as carriers capable of packaging drugs through passive targeting tumor sites by enhanced permeability and retention (EPR) effects. In the present study the biodistribution, pharmacokinetics, micro single-photon emission computed tomography (micro-SPECT/CT) image, dosimetry, and therapeutic efficacy of 188Re-labeled nanoliposomes (188Re-liposomes) in a C26 colonic peritoneal carcinomatosis mouse model were evaluated.Methods: Colon carcinoma peritoneal metastatic BALB/c mice were intravenously administered 188Re-liposomes. Biodistribution and micro-SPECT/CT imaging were performed to determine the drug profile and targeting efficiency of 188Re-liposomes. Pharmacokinetics study was described by a noncompartmental model. The OLINDA|EXM® computer program was used for the dosimetry evaluation. For therapeutic efficacy, the survival, tumor, and ascites inhibition of mice after treatment with 188Re-liposomes and 5-fluorouracil (5-FU), respectively, were evaluated and compared.Results: In biodistribution, the highest uptake of 188Re-liposomes in tumor tissues (7.91% ± 2.02% of the injected dose per gram of tissue [%ID/g]) and a high tumor to muscle ratio (25.8 ± 6.1) were observed at 24 hours after intravenous administration. The pharmacokinetics of 188Re-liposomes showed high circulation time and high bioavailability (mean residence time [MRT] = 19.2 hours, area under the curve [AUC] = 820.4%ID/g*h). Micro-SPECT/CT imaging of 188Re-liposomes showed a high uptake and targeting in ascites, liver, spleen, and tumor. The results were correlated with images from autoradiography and biodistribution data. Dosimetry study revealed that the 188Re-liposomes did not cause high absorbed doses in normal tissue but did in small tumors. Radiotherapeutics with 188Re-liposomes provided better survival time (increased by 34.6% of life span; P < 0.05), tumor and ascites inhibition (decreased by 63.4% and 83.3% at 7 days after treatment; P < 0.05) in mice compared with chemotherapeutics of 5-fluorouracil (5-FU).Conclusion: The use of 188Re-liposomes for passively targeted tumor therapy had greater therapeutic effect than the currently clinically applied chemotherapeutics drug 5-FU in a colonic peritoneal carcinomatosis mouse model. This result suggests that 188Re-liposomes have potential benefit and are safe in treating peritoneal carcinomatasis of colon cancer.Keywords: biodistribution, dosimetry, 5-fluorouracil, micro-SPECT/CT, 188Re-liposome

Thermodynamic and Electrochemical Studies of Niobium in Molten Fluorides and Chloroaluminates

The oxide chemistry of niobium(V) has been studied in molten LiF-BeF2 mixtures. The stoichiometry of an oxygen-containing niobium(V) species (NbO2F) has been established in molten Li2BeF4 from the heterogeneous equilibrations of NiNb2o6 and NiO with the melt containing NiF2, the equilibrium quotient for the reaction was determined. The equilibrium quotient for the heterogeneous reaction of Nb2O5 and BeO with molten LiF-BeF2 mixtures (67-33 and 52-48 mole %) was also determined, and the effect of the melt composition on the solubility of Nb2O5(c) and on the activity coefficient of NbO2F(d) have been examined. The free energies of formation of NbO2F(d) and NiNb2O6(c) has been estimated from the experimental results. A Pourbaix diagram for niobium in molten Li2BeF4 at 500° and a phases diagram at 600° involving NbO2F and NiF2 and the equilibrium oxide phases (Nb2O5, NiNb2O6, NiO, and BeO) in molten Li2BeF4 were constructed. The electrochemical reduction of Nb(V) in molten LiF-BeF2-ZrF4 (65.6-29.4-5.0 mole %) has been studied by linear sweep voltammetry with pyrolytic graphite and platinum electrodes. Potentials were measured with respect to a Ni(II) (saturated)/Ni reference electrode. Nb(V) was found to form NbO2F. The results at the pyrolytic graphite electrode were reproducible; three reduction steps were observed at low scan rates (\u3c 0.5 V/sec) and one reduction step was observed at high scan rates (\u3e 5 V/sec). Mechanisms are proposed for the reduction of niobium(V). The results with platinum electrode were complicated and irreproducible. The electrochemical reduction of Nb(V) chloride and Nb(V) oxychloride in molten AlCl3-NaCl mixtures (63-37 to 50-50 mole %) has been examined by means of chronoamperometry, differential pulse polarography, chronopotentiometry and linear sweep voltammetry using platinum and tungsten electrodes. Potentials were measured with respect to an Al(III) (AlCl3-NaCl, 63-37 mole %)/Al reference electrode. The effect of the melt composition, temperature and Nb(V) concentration on the reduction steps was studied. The results show that the stability of the niobium species and the electrode reduction mechanisms of Nb(V) chloride and oxychloride are very sensitive to the melt composition and to the temperature. The number of reduction steps, the redox potentials, and the stability of various niobium species at different melt compositions and temperatures are reported. Reduction mechanisms of niobium(V) chloride and oxychloride are proposed. Some vibrational spectroscopic studies of solid Nb2O5 and NiNb2O5 were performed; the results indicate that the symmetric stretching frequencies of Nb-O in Nb2O5 and NiNb2O6 are 992 and 882 cm-1, respectively

Translating Research for the Radiotheranostics of Nanotargeted 188Re-Liposome

Nanoliposomes are one of the leading potential nano drug delivery systems capable of targeting chemotherapeutics to tumor sites because of their passive nano-targeting capability through the enhanced permeability and retention (EPR) effect for cancer patients. Recent advances in nano-delivery systems have inspired the development of a wide range of nanotargeted materials and strategies for applications in preclinical and clinical usage in the cancer field. Nanotargeted 188Re-liposome is a unique internal passive radiotheranostic agent for nuclear imaging and radiotherapeutic applications in various types of cancer. This article reviews and summarizes our multi-institute, multidiscipline, and multi-functional studied results and achievements in the research and development of nanotargeted 188Re-liposome from preclinical cells and animal models to translational clinical investigations, including radionuclide nanoliposome formulation, targeted nuclear imaging, biodistribution, pharmacokinetics, radiation dosimetry, radiation tumor killing effects in animal models, nanotargeted radionuclide and radio/chemo-combination therapeutic effects, and acute toxicity in various tumor animal models. The systemic preclinical and clinical studied results suggest 188Re-liposome is feasible and promising for in vivo passive nanotargeted radionuclide theranostics in future cancer care applications