Nanosized multifunctional liposomes for tumor diagnosis and molecular imaging by SPECT/CT.
Among currently used cancer imaging methods, nuclear medicine modalities provide metabolic information, whereas modalities in radiology provide anatomical information. However, different modalities, having different acquisition times in separate machines, decrease the specificity and accuracy of images. To solve this problem, hybrid imaging modalities were developed as a new era, especially in the cancer imaging field. With widespread usage of hybrid imaging modalities, specific contrast agents are essentially needed to use in both modalities, such as single-photon emission computed tomography/computed tomography (SPECT/CT). Liposomes are one of the most desirable drug delivery systems, depending on their suitable properties. The aim of this study was to develop a liposomal contrast agent for the diagnosis and molecular imaging of tumor by SPECT/CT. Liposomes were prepared nanosized, coated with polyethylene glycol to obtain long blood circulation, and modified with monoclonal antibody 2C5 for specific tumor targeting. Although DTPA-PE and DTPA-PLL-NGPE (polychelating amphilic polymers; PAPs) were loaded onto liposomes for stable radiolabeling for SPECT imaging, iopromide was encapsulated into liposomes for CT imaging. Liposomes [(DPPC:PEG(2000)-PE:Chol:DTPA-PE), (PL 90G:PEG(2000)-PE:Chol:DTPA-PE), (DPPC:PEG(2000)-PE:Chol:PAPs), (PL 90G:PEG(2000)-PE:Chol:PAPs), (60:0.9:39:0.1% mol ratio)] were characterized in terms of entrapment efficiency, particle size, physical stability, and release kinetics. Additionally, in vitro cell-binding studies were carried out on two tumor cell lines (MCF-7 and EL 4) by counting radioactivity. Tumor-specific antibody-modified liposomes were found to be effective multimodal contrast agents by designating almost 3-8 fold more uptake than nonmodified ones in different tumor cell lines. These results could be considered as an important step in the development of tumor-targeted SPECT/CT contrast agents for cancer imaging.
Department of Radiopharmacy, Faculty of Pharmacy, Hacettepe University, 06100, Ankara, Turkey.
Mine
M
Silindir
Suna
S
Erdoğan
A Yekta
AY
Özer
A Lale
AL
Doğan
Murat
M
Tuncel
Ömer
Ö
Uğur
Vladimir P
VP
Torchilin
D045744:Cell Line, Tumor; D003287:Contrast Media; D003952:Diagnostic Imaging; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D064847:Multimodal Imaging; D053758:Nanoparticles; D009369:Neoplasms / Q000175:diagnosis* / Q000473:pathology; D010316:Particle Size; D011092:Polyethylene Glycols; D014018:Tissue Distribution
D003287:Contrast Media; D008081:Liposomes; D011092:Polyethylene Glycols