Liposomal nanoparticles are versatile drug delivery vehicles that show great promise in cancer therapy. In an effort to quantitatively measure their in vivo pharmacokinetics, we developed a highly efficient 89 Zr liposome-labeling method based on a rapid ligand exchange reaction between the membrane-permeable 89 Zr(8-hydroxyquinolinate) 4 complex and the hydrophilic liposomal cavity-encapsulated deferoxamine (DFO). This novel 89 Zr-labeling strategy allowed us to prepare radiolabeled forms of a folic acid (FA)-decorated active targeting 89 Zr-FA-DFO-liposome, a thermosensitive 89 Zr-DFO-liposome, and a renal avid 89 Zr-PEG-DFO-liposome at room temperature with near-quantitative isolated radiochemical yields of 98%±1% (n=6), 98%±2% (n=5), and 97%±1% (n=3), respectively. These 89 Zr-labeled liposomal nanoparticles showed remarkable stability in phosphate-buffered saline and serum at 37°C without leakage of radioactivity for 48 h. The uptake of 89 Zr-FA-DFO-liposome by the folate receptor-overexpressing KB cells was almost 15-fold higher than the 89 Zr-DFO-liposome in vitro. Positron emission tomography imaging and ex vivo biodistribution studies enabled us to observe the heterogeneous distribution of the 89 Zr-FA-DFO-liposome and 89 Zr-DFO-liposome in the KB tumor xenografts, the extensive kidney accumulation of the 89 Zr-FA-DFO-liposome and 89 Zr-PEG-DFO-liposome, and the different metabolic fate of the free and liposome-encapsulated 89 Zr-DFO. It also unveiled the poor resistance of all three liposomes against endothelial uptake resulting in their catabolism and high uptake of free 89 Zr in the skeleton. Thus, this technically simple 89 Zr-labeling method would find widespread use to guide the development and clinical applications of novel liposomal nanomedicines.

The combination of early diagnosis and complete surgical resection offers the greatest prospect of curative cancer treatment. An iodine-124/fluorescein-based dual-modality labeling reagent, 124I-Green, constitutes a generic tool for one-step installation of a positron emission tomography (PET) and a fluorescent reporter to any cancer-specific antibody. The resulting antibody conjugate would allow both cancer PET imaging and intraoperative fluorescence-guided surgery. 124I-Green was synthesized in excellent radiochemical yields of 92 ± 5% (n = 4) determined by HPLC with an improved one-pot three-component radioiodination reaction. The A5B7 carcinoembryonic antigen (CEA)-specific antibody was conjugated to 124I-Green. High tumor uptake of the dual-labeled A5B7 of 20.21 ± 2.70, 13.31 ± 0.73, and 10.64 ± 1.86%ID/g was observed in CEA-expressing SW1222 xenograft mouse model (n = 3) at 24, 48, and 72 h post intravenous injection, respectively. The xenografts were clearly visualized by both PET/CT and ex vivo fluorescence imaging. These encouraging results warrant the further translational development of 124I-Green for cancer PET imaging and fluorescence-guided surgery.

Understanding the in vivo behavior of experimental therapeutic cells is fundamental to their successful development and clinical translation. Iodine-124 has the longest half-life (4.2 days) among the clinically used positron emitters. Consequently, this isotope offers the longest possible tracking time for directly labeled cells using positron emission tomography (PET). Herein, we have radiosynthesized and evaluated two iodine-124/fluorescein-based dual PET and fluorescent labeling reagents, namely 124I-FIT-Mal and 124I-FIT-(PhS)2Mal for cell surface thiol bioconjugation. 124I-FIT-(PhS)2Mal labeled cells significantly more effectively than 124I-FIT-Mal. It conjugated to various cell lines in 22%–62% labeling efficiencies with prolonged iodine-124 retention. 124I-FIT-(PhS)2Mal mainly conjugated on the cell membrane, which was confirmed by high-resolution fluorescence imaging. The migration of 124I-FIT-(PhS)2Mal labeled Jurkat cells was visualized in NSG mice with excellent target-to-background contrast using PET/CT over 7 days. These data demonstrate that 124I-FIT-(PhS)2Mal can dynamically track cell migration in vivo using PET/CT over a clinically relevant time frame.