title: Techniques for Loading Technetium-99m and Rhenium-186/188 Radionuclides into Preformed Liposomes for Diagnostic Imaging and Radionuclide Therapy.
abstract: 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 (99mTc), for noninvasive detection of disease and for monitoring the pharmacokinetics and biodistribution of liposomal drugs, and/or with therapeutic beta-emitting radionuclides, rhenium-186/188 (186/188Re), for radionuclide therapy. These efficient and practical liposome radiolabeling methods use a post-labeling mechanism to load99mTc or186/188Re into preformed liposomes prepared in advance of the labeling procedure. For all liposome radiolabeling methods described, a lipophilic chelator is used to transport99mTc or186/188Re across the lipid bilayer of the preformed liposomes. Once within the liposome interior, the pre-encapsulated glutathione or ammonium sulfate (pH) gradient provides for stable entrapment of the99mTc and186/188Re within the liposomes. In the first method,99mTc is transported across the lipid bilayer by the lipophilic chelator, hexamethylpropyleneamine oxime (HMPAO) and99mTc-HMPAO becomes trapped by interaction with the pre-encapsulated glutathione within the liposomes. In the second method,99mTc or186/188Re is transported across the lipid bilayer by the lipophilic chelator, N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA), and99mTc-BMEDA or186/188Re-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 for99mTc or186/188Re to transport the radionuclides across the lipid bilayer. Once within the more acidic liposome interior,99mTc/186/188Re-BMEDA complex becomes protonated and more hydrophilic, which results in stable entrapment of the99mTc/186/188Re-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 with99mTc-BMEDA for noninvasive monitoring of tissue distribution during treatment or with186/188Re-BMEDA for combination chemo-radionuclide therapy.
authors.affiliation: Department of Radiology, MSC 7800, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229-3900, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Goins
authors.affiliation: Department of Radiation Oncology, School of Medicine, Case Western Reserve University/University Hospitals Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH, 44106, USA.
authors.forename: Ande
authors.initials: A
authors.lastname: Bao
authors.affiliation: Department of Radiology, MSC 7800, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229-3900, USA. Phillips@uthscsa.edu.
authors.forename: William T
authors.initials: WT
authors.lastname: Phillips
mesh_terms: D000645:Ammonium Sulfate / Q000737:chemistry; D003952:Diagnostic Imaging / Q000379:methods*; D005029:Ethylenediamines / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry; D015609:Organotechnetium Compounds / Q000737:chemistry; D011868:Radioisotopes / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000737:chemistry*; D012211:Rhenium / Q000737:chemistry*; D013667:Technetium / Q000737:chemistry*; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D051598:Whole Body Imaging
chemical_list: C521828:188Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine; D005029:Ethylenediamines; D008081:Liposomes; D009942:Organometallic Compounds; D015609:Organotechnetium Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C000615079:Rhenium-186; C557969:technetium 99m N,N-bis(2-mercaptoethyl)-N',N'-diethyl-ethylenediamine; D012211:Rhenium; D013667:Technetium; D005978:Glutathione; D000645:Ammonium Sulfate
keywords: Imaging; Liposomes; Nanoparticle; Nuclear medicine; Radiolabeling; Radionuclide; Radiopharmaceutical; Rhenium; Technetium-99m; Theranostic