Techniques for Loading Technetium-99m and Rhenium-186/188 Radionuclides into Pre-formed Liposomes for Diagnostic Imaging and Radionuclide Therapy
Techniques for Loading Technetium-99m and Rhenium-186/188 Radionuclides into Pre-formed Liposomes for Diagnostic Imaging and Radionuclide Therapy
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DOI：
10.1007/978-1-60761-447-0_32
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Phillips, William T.
中科院分区：
文献类型：
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作者：
Goins, Beth;Bao, Ande;Phillips, William T.
Liposomes can serve as carriers of radionuclides for diagnostic imaging and therapeutic applications. Herein, procedures are Outlined for radiolabeling liposomes with the gamma-emitting radionuclide, technetium-99m (Tc-99m), for non-invasive detection of disease and for monitoring the pharmacokinetics and biodistribution of liposomal drugs, and/or with therapeutic beta-emitting radionuclides, rhenium-186/188 (Re-186/188), for radionuclide therapy. These efficient and practical liposome radiolabeling methods use a post-labeling mechanism to load Tc-99m or Re-186/188 into pre-formed liposomes prepared in advance of the labeling procedure. For all liposome radiolabeling methods described, a lipophilic chelator is used to transport Tc-99m or Re-186/188 across the lipid bilayer of the pre-formed liposomes. Once within the liposome interior, the pre-encapsulated glutathione or ammonium sulfate (pH) gradient provides for stable entrapment of the Tc-99m and Re-186/188 within the liposomes. In the first method, Tc-99m is transported across the lipid bilayer by the lipophilic chelator, hexamethylpropyleneamine oxime (HMPAO) and Tc-99m-HMPAO becomes trapped by interaction with the pre-encapsulated glutathione within the liposomes. In the second method, Tc-99m or Re-186/188 is transported across the lipid bilayer by the lipophilic chelator, N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA), and Tc-99m-BMEDA or Re-186/188-BMEDA becomes trapped by interaction with pre-encapsulated glutathione within the liposomes. In the third method, an ammonium Sulfate (pH) gradient loading technique is employed using liposomes; with an extraliposomal pH of 7.4 and an interior pH of 5.1. BMEDA, which is lipophilic at pH 7.4, serves as a lipophilic chelator for Tc-99m or Re-186/188 to transport the radionuclides across the lipid bilayer. Once within the more acidic liposome interior, Tc-99m/Re-186/188-BMEDA complex becomes protonated and more hydrophilic, which results in stable entrapment of the Tc-99m/Re-186/188-BMEDA complex within the liposomes. Since many commercially available liposomal drugs use an ammonium sulfate (pH) gradient for drug loading, these liposomal drugs can be directly radiolabeled with Tc-99m-BMEDA for non-invasive monitoring of tissue distribution during treatment or with Re-186/188-BMEDA for combination chemo-radionuclide therapy.
