96
FDG-PET has strong potential in translational research for therapy-related
assessment in the tumor volume, proliferation and metabolism and drug biodistri-
bution in laboratory animals [ 42 , 43 ], all of which play an important role in estab-
lishing drug efficacy in various malignancies [ 44 – 48 ]. During preclinical stage of
ENK cell therapy program against myeloma, we observed considerably high
uptake in myeloma both within and outside of the human fetal bone implanted
in NOD-SCID/IL2Rynull-hu mice compared to the mice received ENK cells
(Fig. 6.5). However, an obstacle associated with the heterogeneity of glucose
uptake in various areas of a tumor was reported for PET in preclinical studies
which could not be correlated with standard caliper assessments to assess the
antitumor activity of enzastaurin, a novel protein kinase C-beta II inhibitor in
mouse xenografts [ 49 ]. Unfortunately, due to the spatial resolution limits of the
PET scanner, in FDG-PET imaging, small lesions (<5 mm) may go unnoticed and
may provide false-negative results. [ 17 ]. Likewise, metabolically active areas
after inflammation or infection or from brown fat may show increased activity
leading to false-positive results [ 50 ]. In addition, the FDG-PET imaging
system for small animals is expensive, and is mainly restricted to bigger research
centers [ 23 ].
Despite these limitations, FDG-PET imaging in small animals is a viable option
which allows therapeutic interventions and optimization of treatment, one of the
main goals of preclinical studies.
6.3 Conclusion
Circulating hIg and x-radiography has been conventionally used for the assessment
of tumor burden in mice for preclinical studies in myeloma research. However,
there are drawbacks associated with these approaches. Though, BLI provides the
engraftment pattern, growth dynamics and therapy-related changes in tumor vol-
ume following treatment in xenograft models but it needs genetic modification of
the cells, which is a challenge, for primary myeloma cells. Many of these limita-
tions could be addressed by adoption of novel, non-invasive molecular imaging
techniques such as MRI and FDG-PET. Although, MRI and FDG-PET involves
high cost, availability and requirement of a radio-nucleotide facility, these are use-
ful adjunctive imaging methods, established to evaluate therapeutic response in
preclinical studies. Major advantage and disadvantages for these techniques have
been summarized in Table 6.1.
T.K. Garg and T. Pandey