Technical NoteA cryotrap as flow reactor for synthesis of 211At labelled compounds
Introduction
The α-particle emitter 7.2-h 211At is a prospective candidate for targeted cancer therapy, due to its favourable decay properties. If delivered promptly and strongly bound to the target tissue, it could be a valuable tool for the treatment of microtumours or micrometastases (for a review cf. Weinreich, 1997). Among the astatinated radiotherapeutic compounds, 5-[211At]astato-2′-deoxyuridine (AUdR) acts as a thymidine analogue and is rapidly incorporated into the DNA of proliferating cells (Vaidyanathan et al., 1996). On the other hand, N-succinimidyl-4-[211At]astatobenzoate (SAB) is employed as an intermediate for the selective astatination of tumour targeting proteins (Wilbur et al., 1993).
The astatination of both compounds is performed by destannylation. Generally, the reaction between 211At and a suitable carrier or a surrogate group should be carried out quickly, in a small reaction volume and in minimized contact with any surfaces. By this technique, radiochemical loss caused by radioactive decay, adsorption or undesirable side reactions, is avoided.
211At is produced routinely via the nuclear reaction 209Bi(α, 2n)211At by irradiation of bismuth metal with 28-MeV protons, followed by dry distillation. By this method, 211At can be obtained in a small solvent volume or adsorbed onto a small surface (silver wool) or on a silica gel column, respectively (Weinreich, 1997). Removal from these adsorbents is generally necessary and causes further reaction steps, accompanied by avoidable losses in the radiochemical yield.
In this paper, an easy method for the trapping and consecutive preparation of 211At-labelled compounds in a small volume is presented. This is achieved by the use of an inert capillary, serving simultaneously as cryotrap and reactor, which is compatible with reactions on a μl-scale both in aqueous and organic solvents. It should be mentioned, however, that in the past cryotrapping, which was previously introduced for the separation of 211At, but using ml-volumes of solution or gas, presented certain disadvantages in the successful astatination of proteins or smaller molecules (Meyer and Roessler, 1976; Wilbur et al., 1993). The following method should result in a technically easier and less laborious preparation of astatinated compounds.
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Materials and methods
All reagents were obtained from commercial sources, as analytical reagent grade or better, and were used as delivered. 5-Trimethylstannyl-2′-deoxyuridine (TMSUdR) and N-succinimidyl-4-(trimethylstannyl)benzoic acid (p-MeATE) were synthesized as described previously (Koziorowski and Weinreich, 1997; Koziorowski et al., 1998). Thin layer chromatography (TLC) was performed on precoated silicagel 60 F254 on glass, 5×20 cm (Merck), with ethyl acetate/hexane 1:1 (v/v) as the mobile phase for SAB and
Experimental
Astatine was distilled at 660°C with an air flow of 60 ml/min. The Teflon tube was immersed in an ethanol–liquid nitrogen cooling bath kept at −50°C (Fig. 1). After distillation, the tube was cut in half and one part was used for the synthesis of AUdR and the other for that of SAB. 300 μl ReactiVials (Pierce) were coated with either 20 or 100 μg Iodogen (Pierce) from a 1 mg/ml dichloromethane solution (Guenther et al., 1998).
Results and discussion
The yields (radiochemical, recovery and overall) in 50 μl of each precursor solution, are presented in Table 1. The radiochemical yields for AUdR and SAB were comparable to those reported previously (Hadley et al., 1991; Vaidyanathan et al., 1996). The amount of oxidant (Iodogen) did not influence the radiochemical yield, implying that the lower amount was sufficient to oxidize the astatine completely and that the higher amount did not produce significant adverse effects. The divergent recovery
Acknowledgements
The authors are indebted to Professor Börje Larsson for his continuous interest in this work and Dr M. Simmonds (Neutron Spallation Source, PSI) for productive discussions. The support of the Swiss National Fonds (No. 3100-045665.95/1) is gratefully acknowledged.
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