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due to the lack of sensitivity of CT contrast agents, as well as the potential
toxicity of X-ray contrast agents. However, cells have been passively labeled
in vivo , such as macrophages with iodinated nanoparticles for CT detection
of atherosclerotic plaques in hyperlipidemic rabbits (Hyafil et al . 2007) and
with bismuth sulfide nanoparticles for liver and lymph node imaging in
mice (Rabin et al . 2006). This approach results in substantial accumulation of
radiopaque agents in a focal area.
We have pursued a novel method of making cells X-ray visible, by encap-
sulating cells in semipermeable alginate capsules while loading the capsules
with bismuth sulfide and barium sulfate during the polymerization of the
alginate (Barnett et al . 2006). Encapsulated cell therapy has been widely
pursued for the prevention of immunorejection of transplanted cells, while
enabling incorporation of a high payload of contrast agent to allow detection
of single capsules with MRI (Barnett et al . 2007) and X-ray imaging (Barnett
et al . 2006). Microencapsulation creates a semipermeable membrane that pre-
vents passage of antibodies and complement, thereby preventing graft rejec-
tion (Lim and Sun 1980; Orive et al . 2006). While antibodies are blocked, the
selective permeability of the capsule allows for passage of therapeutic factors
produced by encapsulated cells.
Our radiopaque capsules had a characteristic white appearance for barium
sulfate capsules (Ba X-caps) or yellow for bismuth sulfide capsules (Bi X-caps)
( Figure 17.2 ) . As compared to unlabeled (nonradiopaque) microcapsules, we
found both Ba X-caps and Bi X-caps had equal permeability to fluorescent
lectins with different molecular weights. Capsules were permeable to luo-
rescent lectins smaller than 75 kDa but were impermeable to lectins larger
than 120 kDa, that is, blocking antibodies while allowing penetration of
smaller nutrients and secretion of insulin (MW ~ 5 kDa).
We have successfully imaged radiopaque capsules in mice and rabbits.
Single Ba X-caps and Bi X-caps were clearly identified in vivo after trans-
plantation into the peritoneal cavity of mice ( Figure 17.3 ) and after intramus-
cular injection into the hind limb of rabbits ( Figure  17.4 ) . Two weeks after
injection, both X-caps retained their radiopacity in vivo as compared to day
0 (Figure  17.4). Other recent approaches for making X-ray visible capsules
include the use of PFOB (Barnett et al., 2011) and gold nanoparticles (Kim et
al. 2011).
17.6 Summary and Conclusions
Cellular therapies are likely to become an integrated part of regenerative
medicine, and image-guided injections, based on either CT/X-ray or MRI,
will be needed to advance the clinical field. Studies on image-guided injec-
tions of cellular therapeutics have so far been limited to MRI using SPIO
 
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