Biomedical Engineering Reference
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significantly increased blood circulation half-lives and tumor uptake compared to
previous nanoprobes, though the liver and spleen uptakes were twice as much as the
111
In-ChL6 with no iron oxide. SpeCT imaging of excised tumors 48 h p.i. showed that
the radiolabeled iron oxide probe was delivered to the tumor in sufficient amounts
(14% ID/g) without degradation. Toxicity levels were minimal and only observed at
significantly higher Amf amplitudes of 1300 Oe [58, 59]. Interestingly, with the
increase of size (30-100 nm), although higher thermoablative effect could be observed,
the tumor accumulation of radiolabeled SpIO was significantly decreased [60]. Also,
SpIO was also explored for SpeCT/mR application to study the
in vivo
mapping of
sentinel lymph node (SLN) as a means of staging metastasis in breast cancer and
malignant melanoma via
99m
Tc radiolabeling. The biodistribution showed 100% ID/g
accumulation of
99m
Tc-labeled superparamagnetic iron oxide nanoparticles (SpIONs)
in the SLN and less than 2% ID/g in the liver and spleen, which was also confirmed
by SpeCT/mR images. Autoradiography showed the heterogeneous distribution of
99m
Tc-SpIONs in the lymph nodes [61].
SpIONs with bare or weakly bound coating on their surface can be surface
modified directly with bisphosphonates (bps). bps are drugs that bind strongly to
metabolically active bone as used in oncology and osteoporosis [62]. bp can be
further functionalized with fluorophores, radionuclides, and biological tags, thus
serving as anchor agents on SpIONs [63-65]. A clinically approved, SpIO-based
liver mRI agent, endorem/feridex, was conjugated to a
99m
Tc-bp tracer via the
dipicolylamine-alendronate (DpA-ale) group. The radiolabeled endorem/feridex
showed excellent
in vitro
and
in vivo
stability according to nanoSpeCT while
maintaining its mRI contrast capabilities. This multimodal SpeCT/mRI agent,
99m
Tc-DpA-ale-endorem, showed rapid uptake by the ReS with 96.9 ± 0.9% ID
found in the liver, 1.3 ± 0.4% ID in the spleen, and 1.8 ± 0.7% ID in other organs.
The uptake in bone as measured in the femur was about 2% ID. These values are
in good agreement with the nanoparticle-bound
99m
Tc-DpA-ale showing that the
radiolabeled bp and the nanoparticle colocalized in the ReS organs with little or
no degradation
in vivo
. Due to the versatility of the anchoring agent, bp, radiola-
beled SpIO-based contrast particles can be extended to peT/mRI applications for
accurate quantification of the biodistribution of the contrast agent [62].
7.3.4
Radiolabeled polymeric Nanoparticles for spect imaging
Dendrimers, a member of the polymer nanoparticle construct, have tunable properties
and an elevated capacity for multiple targeting, diagnostic imaging, and therapeutic
agents per molecule. They consist of highly branched monomer units with sizes rang-
ing from 10 to 100 nm. These monomers are synthetically layered upon each other in
a stepwise controlled fashion, resulting in a monodispersed molecular assembly.
Dendrimers contain a core-shell surrounded by layers of covalently linked monomers
called generations (g) with terminal surface groups (Z) [66]. besides their excellent
size, shape, and surface chemistry control, which allow for improved manipulation
of their
in vivo
biodistribution and pharmacokinetics, dendrimers are often soluble,
biocompatible, and nonimmunogenic [66-68]. Similar to other targeting nanoparticles,
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