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 (111)In and (99m)Tc, for single-photon emission computed tomography (SPECT), (68)Ga for positron emission tomography (PET), and (177)Lu for therapeutic applications. PEGylated DTPA-NP with varying DTPA amounts, different composition, and size were radiolabeled with (111)In, (177)Lu, and (68)Ga, using various buffers. (99m)Tc-labeling was performed directly and by using the carbonyl aquaion, [(99m)Tc(H(2)O)(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 (111)In (>4 MBq/mug liposome), followed by (68)Ga and (177)Lu; for (99m)Tc, high labeling yields and SA were only achieved by using [(99m)Tc(H(2)O)(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 (99m)Tc- and (68)Ga, compared to (111)In-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.
Clinical Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria.
Anna
A
Helbok
Clemens
C
Decristoforo
Georg
G
Dobrozemsky
Christine
C
Rangger
Eric
E
Diederen
Brigitte
B
Stark
Ruth
R
Prassl
Elisabeth
E
von Guggenberg
D000818:Animals; D005710:Gallium Radioisotopes; D007205:Indium Radioisotopes; D007553:Isotope Labeling / Q000379:methods*; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics; D008187:Lutetium / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D053758:Nanoparticles / Q000737:chemistry*; D015609:Organotechnetium Compounds; D004369:Pentetic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D011868:Radioisotopes / Q000627:therapeutic use; D019275:Radiopharmaceuticals; D051381:Rats; D011917:Rats, Inbred Lew; D015899:Tomography, Emission-Computed, Single-Photon
D005710:Gallium Radioisotopes; D007205:Indium Radioisotopes; D008081:Liposomes; D015609:Organotechnetium Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D008187:Lutetium; D004369:Pentetic Acid