Zielhuis Sander W, Seppenwoolde Jan-Henry, Mateus Vanessa A P, Bakker Chris J G, Krijger Gerard C, Storm Gert, Zonnenberg Bernard A, van het Schip Alfred D, Koning Gerben A, Nijsen Johannes F W
Department of Nuclear Medicine, University Medical Center, Utrecht, The Netherlands.
Cancer Biother Radiopharm. 2006 Oct;21(5):520-7. doi: 10.1089/cbr.2006.21.520.
Many advanced molecular imaging agents are currently being investigated preclinically. Especially, liposomes, have proven to be very promising carrier systems for diagnostic agents for use in single-photon emission computed tomography (SPECT) or magnetic resonance imaging (MRI), as well as for therapeutic agents to treat diseases such as cancer. In this study, nanosized liposomes were designed and labeled with the radionuclides, holmium-166 (both a beta- and gamma-emitter and also highly paramagnetic) or technetium-99m, and coloaded with paramagnetic gadolinium allowing multimodality SPECT and MR imaging and radionuclide therapy with one single agent.
Diethylenetriaminepentaacetic acid bisoctadecylamide (an amphiphilic molecule with a chelating group suitable for labeling with radionuclides) and gadoliniumacetylacetonate (GdAcAc) (a small lipophilic paramagnetic molecule) were incorporated in liposomes. The liposomes were characterized by measuring their mean size and size distribution, gadolinium content, and radiochemical stability after incubation in human serum at 37 degrees C. The MRI properties (in vitro) were determined by use of relaxivity measurements at 1.5 and 3.0 Tesla in order to evaluate their potency as imaging agents.
The liposomes were successfully labeled with holmium-166, resulting in a high labeling efficiency (95% +/- 1%) and radiochemical stability (> 98% after 48 hours of incubation), and coloaded with GdAcAc. Labeling of liposomes with technetium-99m was somewhat less efficient (85% +/- 2%), although their radiochemical stability was sufficient (95% +/- 1% after 6 hours of incubation). MRI measurements showed that the incorporation of GdAcAc had a strong effect on the MRI relaxivity.
The synthesized liposomes allow for multimodality imaging and therapy, which makes these new agents highly attractive for future applications.
目前许多先进的分子成像剂正在进行临床前研究。特别是，脂质体已被证明是用于单光子发射计算机断层扫描（SPECT）或磁共振成像（MRI）的诊断剂以及用于治疗癌症等疾病的治疗剂的非常有前景的载体系统。在本研究中，设计了纳米级脂质体，并用放射性核素钬-166（既是β发射体又是γ发射体，且具有高顺磁性）或锝-99m进行标记，并共负载顺磁性钆，从而实现用单一制剂进行多模态SPECT和MR成像以及放射性核素治疗。
将二乙烯三胺五乙酸双十八烷基酰胺（一种具有适合用放射性核素标记的螯合基团的两亲分子）和乙酰丙酮钆（GdAcAc）（一种小的亲脂性顺磁性分子）掺入脂质体中。通过测量脂质体在37℃人血清中孵育后的平均大小和大小分布、钆含量和放射化学稳定性来对其进行表征。通过在1.5和3.0特斯拉下进行弛豫率测量来确定MRI特性（体外），以评估它们作为成像剂的效能。
脂质体成功用钬-166标记，标记效率高（95%±1%）且放射化学稳定性好（孵育48小时后>98%），并共负载GdAcAc。用锝-99m标记脂质体的效率略低（85%±2%），尽管其放射化学稳定性足够（孵育6小时后为95%±1%）。MRI测量表明，GdAcAc的掺入对MRI弛豫率有强烈影响。
合成的脂质体可实现多模态成像和治疗，这使得这些新型制剂对未来应用极具吸引力。
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