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Abstract

INTRODUCTION:

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 stable 64Cu incorporation into liposomes.

RESULTS:

PET imaging and biodistribution studies with 64Cu-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.

CONCLUSION:

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.​ 

Author information​

Lee SG1, Gangangari K2, Kalidindi TM3, Punzalan B3, Larson SM4, Pillarsetty NV5.

1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY; Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY.

2Department 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.

3Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY.

4Department 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.

5Department 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.