Copper-64 labeled liposomes for imaging bone marrow.
BACKGROUND
Bone marrow is the soft tissue compartment inside the bones made up of hematopoietic cells, adipocytes, stromal cells, phagocytic cells, stem cells, and sinusoids. While [18F]-FLT has been utilized to image proliferative marrow, to date, there are no reports of particle based positron emission tomography (PET) imaging agents for imaging bone marrow. We have developed copper-64 labeled liposomal formulation that selectively targets bone marrow and therefore serves as an efficient PET probe for imaging bone marrow.


METHODS
Optimized liposomal formulations were prepared with succinyl PE, DSPC, cholesterol, and mPEG-DSPE (69:39:1:10:0.1) with diameters of 90 and 140nm, and were doped with DOTA-Bn-DSPE for stable64Cu incorporation into liposomes.


RESULTS
PET imaging and biodistribution studies with64Cu-labeled liposomes indicate that accumulation in bone marrow was as high as 15.18±3.69%ID/g for 90nm liposomes and 7.01±0.92%ID/g for 140nm liposomes at 24h post-administration. In vivo biodistribution studies in tumor-bearing mice indicate that the uptake of 90nm particles is approximately 0.89±0.48%ID/g in tumor and 14.22±8.07%ID/g in bone marrow, but respective values for Doxil® like liposomes are 0.83±0.49%ID/g and 2.23±1.00%ID/g.


CONCLUSIONS
Our results indicate that our novel PET labeled liposomes target bone marrow with very high efficiency and therefore can function as efficient bone marrow imaging agents.
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY; Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY.
Sang-Gyu
SG
Lee
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Chemistry, Hunter College, The Graduate Center, The City University of New York, New York, NY; Ph. D program in Chemistry, The Graduate Center, The City University of New York, New York, NY.
Kishore
K
Gangangari
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY.
Teja Muralidhar
TM
Kalidindi
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY.
Blesida
B
Punzalan
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY; Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY; Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Radiology, Weill Cornell Medical College, New York, NY. Electronic address: larsons@mskcc.org.
Steven M
SM
Larson
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Radiology, Weill Cornell Medical College, New York, NY. Electronic address: pillarsn@mskcc.org.
Naga Vara Kishore
NVK
Pillarsetty
D000818:Animals; D001853:Bone Marrow / Q000000981:diagnostic imaging* / Q000378:metabolism; D003301:Copper Radioisotopes; D004339:Drug Compounding; D007553:Isotope Labeling; D008081:Liposomes / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D014018:Tissue Distribution
D003301:Copper Radioisotopes; D008081:Liposomes
Bone marrow; Copper-64; DOTA-Bn-DSPE; Liposome; Pet
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