Targeted multimodality contrast agent: Synthesis and applications of 18F-labeled targeted perfluorocarbon-filled albumin microbubbles for microUS and microPET

Targeted albumin shelled microbubbles (MBs) have been applied as a potential drug carrier for the treatment of cancer cells. To provide the pharmacokinetics of the targeted albumin MBs for in vivo therapeutic use of cancer therapy, the multimodality N-succinimidyl-4- [¹⁸F]fluorobenzoate (¹⁸F-SFB) labeled tumor angiogenesis-related vascular endothelial growth factor receptor 2 (VEGFR2) targeted MBs (tMBs) were synthesized and the biologic characteristics of the tMBs in MDA-MB-231 human breast-cancer-bearing mice were investigated with micro-positron emission tomography (microPET) and high frequency ultrasound (microUS). The efficiency of tMBs targeted to tumor vascular was 14.8% rather than MBs in contrast enhanced microUS. The ¹⁸F-labeled tMBs were cleared from blood circulation and accumulated in liver (16.3% ID/g ± 6.8) and lung (5.7 ID/g ±1.6) at 60minutes. Uptake of ¹⁸F-labele tMBs was significantly higher in tumor (1.02% ID/g ± 0.3) than in surrounding muscle tissue (0.4% ID/g ± 0.02) at 60minutes. The findings were confirmed with ex vivo biodistribution study. Therefore, ¹⁸F-SFB labeled VEGFR2-targeted MBs showed specific tumor uptake in human breast-cancer-bearing mice and could be used as a probe for delivery vehicles in cancer treatment. This study provides useful information for the future clinical application of the multimodality material from imaging to therapeutic levels.