A hybrid solution-solid-phase kit-type radioiodination and purification platform

Objectives Instant kits revolutionized the use of 99mTc and made perfusion type radiopharmaceuticals widely available. Unfortunately, comparable methods for the preparation of molecularly targeted iodine-based agents have not been as successful. In order to produce targeted iodine-based radiopharmaceuticals via kit formulations the method must be high yielding, resist radiolysis, produce agents with optimum effective specific activity (ESA) and be amenable to translation for human use with a variety of different substrates. The objective was to develop such a method that incorporates both radiolabelling and purification that does not require the use of HPLC.

Methods Kits were developed by absorbing fluorine rich (fluorous) tin precursors onto a fluorinated solid-support (fluorous capped silica gel). Upon treatment with a solution of 125I and chloramine-T, halogenation renders the product non-fluorous which can be eluted selectively using an ethanol-water mixture into saline in high purity free from unreacted iodine and precursor.

Results A series of kits designed to produce radioiodinated aryl and heterocyclic derivatives including SIB and MIBG were developed and the products obtained in high radiochemical purity (>95%) and high radiochemical yields (>80%) and ready for injection without further purification. The optimal loading levels, elution system and solid-support were developed during the course of this work.

Conclusions A new single step radioiodination and purification platform that is easily automated and suitable for kit-like production of iodine-based agents was developed. The reported hybrid solution-solid-phase strategy overcomes some of the limitations of previously reported solution, fluorous and purely solid-phase labeling methods.

Research Support Canadian Institutes of Health Research, Canadian Cancer Society, Ontario Institute for Cancer Research, Natural Sciences and Engineering Research Council of Canada.