A fast kit preparation of ^123/131I-MIBG by microwave heating

Abstract

1899

Objectives: ^123/131I-MIBG can be synthesized by the following nucleophilic exchange reactions: Cu²⁺ catalyzed reactions in aqueous medium, (NH₄)₂SO₄ solid state transfer catalyst method, reaction in the pseudo melt phase in absence of any catalyst, and a Cu⁺ assisted reaction. Most of these reactions use high reaction temperature and long heating time. Under these reaction conditions, both radiochemical purity and labeling efficiency are reduced. The Cu⁺ assisted nucleophilic exchange reaction is the mildest one; we have used it to prepare ¹²³I-MIBG. When heated at 100°C for 30-40 min, the radiochemical yield is > 99%. Microwave heating has been used to accelerate chemical reactions. We hypothesized that microwave heating may be used for rapid preparation of radioiodinated MIBG. We set out to prepare ^123/131I-MIBG using the Cu⁺ assisted kit method and microwave heating.

Methods: To a septum closed v-vial containing 1 mg cold MIBG, 25 μg CuSO₄.5H₂O and an excess of reducing agents (0.4 mg SnSO₄, 5 mg gentisic acid) in 0.5 ml oxygen-free water, was added 0.1-0.5 ml of oxygen free ^123/131I NaI solution (MDS Nordion, ON, Canada, or Mallickrodt, MO, USA) containing the required activity. The vial was heated in a domestic microwave oven (Kenmore, Model 565,8824581, 2450MHz, 1580W) for 3 min. The labeling efficiency and radiochemical purity were determined by HPLC using μBondPak C₁₈ 3.9×300 mm column (Waters Corporation, MA, USA), 0.1%H₃PO₄/EtOH (80:20) as the mobile phase, and monitoring by UV and radiation detectors.

Results: When the reaction vial was heated in the domestic microwave oven for 3 min, the labeling efficiency was ~100%, and the radiochemical purity was ~100%. Due to the shorter heating time, the microwave heating method significantly reduces radiochemical and chemical impurities.

Conclusions: ^123/131I-MIBG can be quickly prepared in 3 min using microwave-assisted heating with very high radiochemical purity and very high labeling efficiency. Microwave-assisted heating is expected to extend to the preparation of other ^123/125/131I radiopharmaceuticals using the Cu⁺ assisted kit method.