Radiolabeling of lipid-based nanoparticles for diagnostics and therapeutic applications: a comparison using different radiometals

Radiolabeling of nanoparticles (NPs) has been performed for a variety of reasons, such as for studying pharmacokinetics, for imaging, or for therapy. Here, we describe the in vitro and in vivo evaluation of DTPA-derivatized lipid-based NP (DTPA-NP) radiolabeled with different radiometals, including In-111 and Tc-99m, for single-photon emission computed tomography (SPECT), Ga-68 for positron emission tomography (PET), and Lu-177 for therapeutic applications. PEGylated DTPA-NP with varying DTPA amounts, different composition, and size were radiolabeled with In-111, Lu-177, and Ga-68, using various buffers. Tc-99m-labeling was performed directly and by using the carbonyl aquaion, [99mTc(H2O)(3) (CO)(3)](+). Stability was tested and biodistribution evaluated. High labeling yields (> 90%) were achieved for all radionuclides and different liposomal formulations. Specific activities (SAs) were highest for In-111 (> 4 MBq/mu g liposome), followed by Ga-68 and Lu-177; for 99mTc, high labeling yields and SA were only achieved by using [99mTc(H2O)(3) (CO)(3)](+). Stability toward DTPA/histidine and in serum was high (> 80 % RCP, 24 hours postpreparation). Biodistribution in Lewis rats revealed no significant differences between NP in terms of DTPA loading and particle composition; however, different uptake patterns were found between the radionuclides used. We observed lower retention in blood (< 3.3 % ID/g) and lower liver uptake (< 2.7 % ID/g) for Tc-99m- and 68Ga, compared to In-111-NP (blood, < 4 % ID/g; liver, < 3.6 % ID/g). Imaging potential was shown by both PET magnetic resonance imaging fusion imaging and SPECT imaging. Overall, our study shows that PEGylated DTPA-NP are suitable for radiolabeling studies with a variety of radiometals, thereby achieving high SA suitable for targeting applications.