Neutron Activation Preparation of 166Ho-Albumin Microspheres as a Promising Radiopharmaceutical for Tumor Therapy

Abstract

A procedure of activation with thermal neutrons of 165 Ho incorporated in the particle matrix was developed for preparing human blood albumin microspheres (AMs) labeled with 166 Ho. Since the specific activity of 166 Ho-AMs depends on the content of stable 165 Ho in AMs, the features of incorporation of stable holmium in the AM matrix were studied. The content of 165 Ho in AMs was determined by neutron activation analysis. It was found that 165 Ho is incorporated in the solid matrix in the course of its preparation by thermal denaturation of albumin in vegetable oil. The concentration of 165 Ho in AMs increases with increasing initial content of Ho 2 O 3 in olive oil. With increasing particle size, the content of 165 Ho in AMs also increases and reaches a maximum (60%) in the fraction of AM particles with a diameter of 40 3 60 mm prepared at the highest content of Ho 2 O 3 in the olive oil of 3.575 mg ml !1 . Thus, the coarser the AM fractions, the more active preparation will be obtained upon irradiation with thermal neutrons.Search for radiopharmaceuticals (RPs) and evaluation of their specific properties are the main problems of radiopharmaceutics, and the most urgent problem is the choice of the best carriers for selective transport of radionuclides with the optimal nuclear-physical characteristics to the center of tumor or nonneoplastic diseases. The carriers used today in radionuclide therapy can be subdivided into two types: soluble and insoluble (microparticles) compounds. Microspheres are characterized by higher specific uptake in organs and tissues; this process can be controlled by changing physicochemical properties of microparticles and by varying procedures of their administration. First, microparticles labeled with 198 Au were used for therapy of lung carcinoma [1]. Artificial plastic microspheres labeled with 90 Y were unstable, and this problem was solved by preparation of glass microspheres [2]. Glass microspheres are very stable [3], but, having high density (r 3.29 g cm 33 ) [4], they precipitate in the circulatory system [5]. A significant disadvantage of glass microspheres is their resistance to metabolism [6, 7]. Various polymeric resins (such as Bio-Rex 70, Cellex-P, Chelex 100, Sephadex SP, AG 50W-X8, etc. [8]) were used to prepare microparticles, and the best results were obtained with microspheres of Bio-Rex 70 resin labeled with 90 Y [9]. The microspheres prepared from Aminex A-5 polymer and labeled with 166 Ho also gave good results [7]. The results of clinical trials of microspheres prepared from various resins are comparable with those obtained with glass microspheres.Poly-L-lactic acid is the optimal polymer for preparing microspheres; its density is close to that of blood and it is metabolized in the living body. Microspheres of poly-L-lactic acid labeled with 166 Ho can be obtained by incorporation of stable 165 Ho in the particles and by subsequent irradiation with thermal neutrons [6,10]. However, these particles are unstable to irradiation with thermal neutrons at high fluxes ...

Radiochemistry and radiopharmaceuticals

“…Also polydentate ligands with assorted oxygen or sulfur, nitrogen or phosphorus atoms, 135 such as aminodiphosphines, 144 readily form bifunctional chelate complexes with radio-rhenium. This similarity also extends to the use of the tricarbonyl[ 188 Re]rhenium(I) trihydrate cation in complex formation, despite its being more difficult to make than its technetium analogue; many new preparative routes [200][201][202] have been reported. The types of bifunctional ligands, and the types of biomolecules labelled are exactly the same as for technetium.…”

“…Samarium-153 can be chelated by phenyl derivatives of DTPA 117 or by 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid; 187 the latter forms a radiopharmaceutical that can be used in bone pain relief. A technique has been developed for the labelling 188 of human blood albumen with holmium-166. Lutecium-177 is being investigated as a beta emitter that can be used for targeted radiotherapy.…”

“…139,156,157,160,162 A rather simpler procedure (but what the rhenium is doing is less clearly defined) is the reported 'direct' labelling 203 of anti-CD20 with rhenium-188 for use in radioimmunotherapy. Other simple 'labelling' techniques have been described for the preparation of [ 188 Re]rhenium sulfide suspensions, 204 [ 188 Re]-human serum albumin microsheres 205 and [ 188 Re]-polyacrylamide modified magnetic nanoparticles. 206 The latter to be used for magnetically targeted radiotherapy.…”

Pharmacokinetics of a new radiopharmaceutical based on alubmin microspheres and palladium-103 and modified by heat and radiation

“…Then AMS were labeled with the radionuclides holmium-166 [7,8]; rhenium-188 [9,10], and palladium-103 ( 103 Pd) [11,12] in order to create radiopharmaceuticals for radionuclide therapy of tumors. More and more attention is currently being focused on the radioactive isotope 103 Pd [13 -15].…”