Ultrasound/SPECT dual-modality imaging platform using 99mTc-labeled microbubbles

Objectives The objective of this project was to label streptavidin coated microbubbles (MBs) with ^99mTc so that the product could be used in dual modality imaging studies employing ultrasound and SPECT/CT. Radiolabeled MBs can be utilized to determine the in vivo biodistribution of microbubbles; an important aspect of MB technology.

Methods The process is based on the expedient synthesis and purification of a small biotin analogue and the radiolabeling of this ligand with the ^99mTc-tricarbonyl core for SPECT imaging. The labeling reaction is quantitative using microwave assisted heating for 3 minutes at 130 C, with excess unlabeled ligand removed by HPLC purification. High specific activity microbubbles are generated through the use of a novel approach employing streptavidin coated magnetic nanoparticles to scavenge unbound radioligand.

Results Following the synthesis and HPLC purification of the ^99mTc-biotin complex in quantitative yield, radiolabeling of the MBs proceeds such that 65% of the activity was bound to the bubbles according to size exclusion chromatography. The subsequent scavenging of the remaining unbound radioligand through application of streptavidin coated magnetic nanoparticle separation yielded MBs with radiochemical purity of >97%.

Conclusions A new method for the synthesis and purification of ^99mTc-labeled microbubbles has been developed. The synthetic strategy can be used to generate labeled forms of non-targeted and targeted bubbles for use with dual modality ultrasound and SPECT/CT studies.