Radio-labeled Nanoparticles for Biomedical Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 193

liposome-incorporated polychelating amphiphilic polymer (pAp), which resulted in
better and faster gamma-imaging compared to nontargeted liposomal controls [53].
Liposomes labeled with 99m Tc have also shown promise in monitoring therapeutic
drug delivery. In one such study, 99m Tc was introduced into the aqueous layer of
liposomes of similar size and composition to the drug Doxil, a pegylated lipo-
somal-encapsulated form of doxorubicin. mice were injected with either the
99m Tc-labeled liposome, Doxil, or both with subsequent quantification of tumor
delivery post-hyperthermia treatment. This allowed visualization of the drug's effec-
tiveness in reaching its target site [54]. In another study, the pharmacokinetics of
intratumoral injections of liposomal-based drugs was quantified with 99m Tc-labeled
liposomes. Rat head and neck tumors had intratumoral injections of either 99m Tc-
labeled liposomes or a 99m Tc-labeled small-molecule N,N-bis(2-mercaptoethyl)-N′,
N′-diethylethylenediamine (bmeDA). At 20 h p.i., the liposomal-encapsulated 99m Tc
showed a greater tumor retention (39.2 ± 10.6%, n = 4) compared to the unencapsulated
form (18.7 ± 3.3%, n = 3) [55]. Additionally, better intratumoral 99m Tc activity diffusion
was observed for 99m Tc-liposomes when compared with 99m Tc-bmeDA as shown
in the pinhole microSpeCT images.
Radiolabeled liposomes can also be used to monitor therapeutic drug delivery
to infection sites. 99m Tc was radiolabeled on liposomes using the chelator
N -hydroxysuccinimidyl hydrazine nicotinate hydrochloride (HYNIC), which was
first conjugated to the liposome and then incubated with the 99m Tc. This robust
labeling did not require subsequent purification. High retention at the disease site
was observed (1.74 ± 0.38% ID/g, 24 h post injection) with minimal uptake in the
kidney. This new labeling technique showed better in vitro and in vivo stability as
compared to an older chelation approach using hexamethylpropyleneamine oxime
(HmpAO)-liposome [56].
Researchers have taken advantage of the multifunctional capabilities of liposomes.
Zielhuis et al . successfully labeled liposomes with both a SpeCT radiotracer, either
99m Tc or 166 Ho, and paramagnetic gadolinium. In addition to SpeCT imaging, these
multilabeled liposomes allowed for measurements of mRI relaxivity. potential thera-
peutic advantages could be seen from the beta emissions of 166 Ho. Thus, a single lipo-
some could effectively offer two different imaging modalities as well as therapeutic
gains [57].

7.3.3 Radiolabeled iron oxides for spect imaging

Iron oxide, a member of the inorganic nanoparticle construct, has garnered attention
due to its magnetic properties as well as it low toxicity in humans. Under the influence
of an external alternating magnetic field (Amf), iron oxide exhibits thermoablative
properties and thus, when targeted to solid tumors, can be used in a therapeutic manner.
De Nardo et al . looked at 111 In-DOTA-labeled chimeric L6 (ChL6) mAb conjugated to
pegylated, dextran-coated, 20 nm superparamagnetic iron oxide (SpIO) particles with
one to two mAbs per nanoparticle. The study included considerations of radioimmu-
notargeting, therapeutic potential, and toxicity of the immunotargeted iron oxide nano-
probe in mouse breast cancer xenografts. This immunotargeted nanocarrier showed