186Re/188Re labeled polypeptide microspheres as a potential radiation synovectomy agent

Polypeptide microspheres containing polycysteine crosslinked with polylysine were prepared and radiolabeled with¹⁸⁶Re and¹⁸⁸Re. High labeling yields with the microspheres with both¹⁸⁶Re and¹⁸⁸Re (97%) were obtained, and above 99% retention of radiolabels in water in 24 hours was obtained. Rhenum-186 labeled polycysteine and polylysine microspheres (11 ratio, 20 m as mean diameter) were injected intra-articularly into the rear stifes (knee joints) of normal New Zealand white rabbits. About 87% of injected dose was retained in rabbit stifles and adjacent tissues in 96 hours after injection, while most of the activity lost from the joints was excreted in the urine. Due to its simplicity of preparation and radiolabeling, versatility, and biodegradability, this type of conjugate system may become the therapeutics of choice for radiation synovectomy.     

The decay of188Re

The -ray spectra of¹⁸⁸Re decay have been studied by using two Ge/Li/ spectrometers and a three parameters /E-E-T/ List coincidence system. The energies and relative intensities of 52 -rays and cascade relations of 14 -rays are determined. Ten new -rays: 155 /633–478/, 984, 1096, 1463, 1332, 1530, 1574, 1810, 1867, and 1937 keV have been identified. The 155 /633–478/ transition is confirmed and its relative intensity is estimated by means of coincidence experiment. 24 levels of¹⁸⁸Re are assigned. Among those, 6 levels are first put into the decay scheme of¹⁸⁸Re. In addition to 1443 keV and 1937 keV levels, 1685, 1729 and 1965 keV levels are also observed in the decay of¹⁸⁸Ir and other reaction studies. The 1948 level is recently suggested in the¹⁹⁰Os/p, t/¹⁸⁸Os reaction. The 486 keV and 811 keV -transitions are also put into the level scheme of¹⁸⁸Re. The ^– decay branching ratio is deduced.     

Separation of Clinical Grade 188Re from 188W Using Polymer Embedded Nanocrystalline Titania

Currently, ¹⁸⁸Re is obtained from ¹⁸⁸W/¹⁸⁸Re chromatographic generator containing alumina which has a limited capacity (~80 mg Wg^?1) for ¹⁸⁸W. This results in high bolus volumes of ¹⁸⁸Re, which often needs to be concentrated before radiolabeling. We have demonstrated the feasibility of using polymer embedded nano crystalline titania (TiP), a novel high capacity sorbent material (~300 mg Wg^?1), for developing a ¹⁸⁸W/¹⁸⁸Re chromatographic generator. A TiP based chromatographic ¹⁸⁸W/¹⁸⁸Re generator was developed in which ¹⁸⁸Re could be eluted with 0.9% saline solution. About 90% of the ¹⁸⁸Re could be recovered in the first 4–5 mL of total activity with more than 80% yield. The purity of ¹⁸⁸Re is adequate for clinical applications.     

Separation of Clinical Grade 188Re from 188W Using Polymer Embedded Nanocrystalline Titania

Currently, ¹⁸⁸Re is obtained from ¹⁸⁸W/¹⁸⁸Re chromatographic generator containing alumina which has a limited capacity (~80 mg Wg⁻¹) for ¹⁸⁸W. This results in high bolus volumes of ¹⁸⁸Re, which often needs to be concentrated before radiolabeling. We have demonstrated the feasibility of using polymer embedded nano crystalline titania (TiP), a novel high capacity sorbent material (~300 mg Wg⁻¹), for developing a ¹⁸⁸W/¹⁸⁸Re chromatographic generator. A TiP based chromatographic ¹⁸⁸W/¹⁸⁸Re generator was developed in which ¹⁸⁸Re could be eluted with 0.9% saline solution. About 90% of the ¹⁸⁸Re could be recovered in the first 4–5 mL of total activity with more than 80% yield. The purity of ¹⁸⁸Re is adequate for clinical applications.

     

High specific activity 186Re and 188Re perrhenates to be used for biomolecule labeling

¹⁸⁶Re and ¹⁸⁸Re, two strong beta- and weak gamma-emitters having short half-lives, are intensely studied as promising radionuclides for radiotherapy. Their use for biomolecule labeling is mainly due to their similar behavior with ^99mTc. This paper presents the irradiation operations in a 14 MW Triga SSR Reactor, the chemical processing for obtaining a perrhenate solution of high activity and the final characterization of the products.     

Synthesis of amino-modified magnetite nanoparticles coated with Hepama-1 and radiolabeled with 188Re for bio-magnetically targeted radiotherapy

Summary  Elérh     

Preparation of186Re labeled immunoglobulins: Direct and indirect methods

Kits were developed for labeling sulphur microcolloids with^99mTc. The microcolloids were prepared to get the desired particle size. The stannous chloride was treated with sulphide ions released from thioacetamide in the presence of carboxymethyl cellulose and the pH of the reaction was adjusted to 3.0. The contents of single reaction vial were reacted with^99mTc, the radiochemical yield was higher than 95%. Sulphur-microcolloid kits were stable and the stability was followed for 6 hours. The freeze-dried kits were followed more than three months after production and were found stable. Bone marrow uptake in rabbits was determined to be about 36%. The preparation of^99mTc-sulphur microcolloid is performed in single step process and axellent node scintigraphy was obtained using experimental animal.     

An improved synthesis of S-benzoyl mercaptoacetyltriglycine as BFCA and the labeling of IgG with carrier-free 188Re

S-benzoyl mercaptoacetyltriglycine (S-Bz-MAG₃) was synthesized and labeled with carrier-free ¹⁸⁸Re. The overall yield of S-Bz-MAG₃ is higher than those published in the literature. Dependence of the labeling yield of ¹⁸⁸Re-MAG₃ upon concentration of reducing agent, pH, reaction time, and other parameters was examined and optimum conditions were obtained. The labeling yield of ¹⁸⁸Re-MAG₃ was more than 98%. The concentration procedure was succeeded with Sep-Pak C18 column to obtain highly concentrated ¹⁸⁸Re-MAG₃. The experimental conditions of labeling of IgG with carrier free ¹⁸⁸Re via S-Bz-MAG₃ as a bifunctional chelating agent (BFCA) by pre-radiolabeling of the chelate was studied. The conjugation conditions were optimized. The stability of ¹⁸⁸Re-MAG₃-IgG in vitro was high. The results of this studiy may be useful for ¹⁸⁸Re labeling of MAbs for radioimmunotherapy.     

A new technique for labeling of Lipiodol with 188Re in the treatment of hepatic tumor

A new method for the synthesis of ¹⁸⁸Re-Lipiodol without using a chelating agent and to evaluate the stability and biodistribution of the new agent in rats with hepatic tumors was attempted. Eighteen male Sprague -Dawley rats with liver tumors were sacrificed at 1, 24, and 48 hours (six rats at each time) after injection of approximately 7.4 MBq (0.2 mCi) of ¹⁸⁸Re Lipiodol via the hepatic artery. Samples of tumor, liver and other organs were collected and tissue concentration (%ID/g) of the markers were calculated. Our data showed a high level of radioactivity in the hepatic tumors at every time of the study. The ratios of tumor to normal liver tissue concentration (T/N ratio) were 7.62 at 1 hour, 8.03 at 24 hours, and 7.70 at 48 hours. Except for the liver, kidneys and lungs, concentrations in other organs were low. The new method for labeling Lipiodol with ¹⁸⁸Re is simple and has potential for the treatment of hepatic tumors This revised version was published online in July 2006 with corrections to the Cover Date.     

Production of carrier-free 188Re in the past ten years in Taiwan

Twenty clinical scale alumina-based ¹⁸⁸W/¹⁸⁸Re generators and carrier-free ¹⁸⁸Re has been produced at the Institute of Nuclear Energy Research (INER-Taiwan) for over ten years. 2845.6 GBq (76.9 Ci) of ¹⁸⁸Re-perrhenate solution has been eluted from generators during the past ten years. We have used the harvesting ¹⁸⁸Re solution for labeling radiopharmaceuticals, such as ¹⁸⁸Re-HEDP, ¹⁸⁸Re-MDP, ¹⁸⁸Re-microsphere, ¹⁸⁸Re-lipiodol, and ¹⁸⁸Re-sulfur colloid, etc. The average eluting yield of ¹⁸⁸Re is 78.6±5.8% that was investigated at 1115 harvesting times from 20 generators. Each generator can be used more than six months but the Millipore needs to be changed every two months for smooth harvesting and high yield of ¹⁸⁸Re solution.     

Peptide labeling using 188Re, 188Re-MAG3 and 153Sm-H1ETA: A comparison on their in vitro lipophilicity

Lanreotide peptide was labeled with ¹⁵³Sm-H₁ETA and ¹⁸⁸Re-MAG₃ in order to evaluate whether or not their conjugation to the peptide produce significant differences of the in vitro lipophilicity with respect to the ¹⁸⁸Re-lanreotide prepared by the direct labeling method (highly lipophilic). The differences of lipophilicity between the complexes, were evaluated using a reverse phase HPLC system. The measured lipophilicity of ¹⁵³Sm-H₁ETA-lanreotide, ¹⁸⁸Re-MAG₃-lanreotide and ¹⁸⁸Re-lanreotide was taken to be the capacity factor [k" = (t _R-t ₀)/t ₀ where t _R is the retention time and t ₀ is the dead time] for each of the complexes under identical chromatography conditions. Results showed that the in vitro lipophilicity decreased in the order ¹⁸⁸Re-lanreotide (direct labeling), ¹⁸⁸Re-MAG₃-lanreotide and ¹⁵³Sm-H₁ETA-lanreotide. Since the last one has a capacity factor (k") similar to that of ¹⁸⁸Re-MAG₃, some renal elimination for ¹⁵³Sm-H₁ETA-lanreotide could be expected, which probably would reduce the unnecessary radiation dose to normal tissues.     

Vascular responses to endovascular irradiation of 188Re in the rabbit model after angioplasty

The effects on vascular restenosis of intravascular radiation delivery from ¹⁸⁸Rhenium (Re)-perrhenate liquid-filled balloon through beta-particle radiation are controversial. To determine the effect of beta-radiation on vascular injury in hypercholesterolemic rabbits, thirty rabbits fed with a high cholesterol diet were enrolled into this study. All the rabbits underwent percutaneous transluminal balloon overstretch over left iliac artery. After balloon overstretch, the catheter was withdrawn and immediately followed by irradiation using low dose ¹⁸⁸Re solution (10 Gray) in the vascular wall 0.5 mm distal to intimal surface. After 2 and 6 weeks, arteries were harvested for histological and immunological analysis. This rabbit study suggest that endovascular ¹⁸⁸Re low dose irradiation at the non-injury segment of iliac artery may enhance intima hyperplasia and smooth muscle cell proliferation.     

Comparative studies on radiolytic degradation of deuterium labeled and unlabeled tributyl phosphates

Deuterium labeled tributyl phosphates were synthesized and their solutions in n-dodecane have been investigated for γ-radiolytic degradation up to an absorbed dose of 2,000 kGy from a ⁶⁰Co source. The performance was compared with undeuterated TBP. Radiolysis extent and pattern of formation of major degradation products, viz. dibutyl hydrogen phosphate and monobutyl dihydrogen phosphate were found to be very similar from deuterated or undeuterated samples. Extraction behavior for UO₂ ²⁺ and Pu(IV) was studied after the radiolysis, and the results showed similarity in extraction/stripping behavior for all labeled or unlabeled TBP samples. The isotope effect (k _H/k _D) observed is minimal in this γ-radiolytic degradation study.     

Electron spin resonance studies of spin labeled alternating functional copolymers

The spin-labeled and spin-probed alternating copolymers of poly(phenylvinyl alkyl ethers) with various alkyl groups (Me, Et, sec-Bu) in the ether moiety were investigated by electron spin resonance (ESR). Measurements were taken in different solvents over a wide range of concentration. Studies reveal that the molecular motion of spin-labels and spin-probes depends on the bulkiness of the alkyl group at the solvent concentration in which the effect of segmental rotation is dominant. The implication of the type of chemical bonding on the nitroxide motion is discussed.     

TDDFT studies of absorption and SERS spectra of pyridine interacting with Au20

We present time dependent density functional theory (TDDFT) calculations for a tetrahedral Au20 complex interacting with pyridine for the purpose of modeling absorption and surface enhanced Raman scattering, with emphasis on chemical and electrodynamic enhancement effects. These calculations are done using the ADF code with the BP86 functional, the zeroth-order regular approximation and with the resonant electronic response modeled using a short time approximation expression for the perturbed density matrix, with a damping factor that is empirically chosen. The absorption spectrum of bare Au20 shows strong intraband (sp-sp) and interband (sp-d) coupling with a low-energy peak at 2.89 eV that is mostly intraband and other peaks at 3.94 and 4.70 eV that have mixed intra- and interband character. SERS spectra are calculated for pyridine/Au20 for both vertex (V) and surface (S) configurations at their respective lowest energy absorption maxima (near 2.89 eV), and we find that the V configuration has higher intensities that correspond to SERS enhancements of 10(3)-10(4), whereas S has an enhancement of 10(2)-10(3). These enhancement values are significantly lower than the analogous results for pyridine/Ag20 primarily because of reduced oscillator strength associated with the intraband transition in Au20. Decomposition of the pyridine/Au20 enhancement factor into chemical and electromagnetic contributions (through an analysis of the static SERS intensities) shows enhanced chemical enhancements compared to Ag20 but reduced electromagnetic enhancements.     

Production of positron emitters and application of their labeled compounds to plant studies

The positron emitters¹¹C,¹³N and¹⁸F and their labeled compounds have been produced for studies on plants using a newly developed positron emitting tracer imaging system. Although this system covers, at present, a limited area in a plant, the distribution of the positron emitter fed into the plant can be visualized dynamically. Further development of positron-emitter-labeled compounds is expected to elucidate the physiological function of plants in vivo.