89and labor intensive to attempt luciferase transfection. Although enzyme-linked
immunosorbent assay (ELISA) for human immunoglobulins (hIg) in murine sera
can be used for measuring myeloma burden (provided non-secretory myeloma cases
are not utilized), a non-invasive and real time method of assessing tumor involve-
ment would certainly be of advantage. In this respect MRI combined with FDG-
PET imaging can be of immense potential. While MRI can help determine the
anatomical locations; extent of tumor involvement and tumor burden FDG-PET
scans are sensitive for early tumor detection, evaluation of recurrence and provide
biochemical information concerning tumor metabolism, replication rate, ischemia
levels, and other physiological information.
In the following sections we will discuss role of these techniques in evaluation of
myeloma tumor burden and shall focus on our experience about live imaging using
MRI/PET for the assessment of tumor burden after ENK-cell therapy in a mouse
model for myeloma and how this technique can be successfully used for drug-
related and/or cytotherapy-associated evaluation in small animals.
6.2 Current Methods for Assessment of Tumor Burden
in Murine Model of hu-myeloma
Animal models have played a major role in understanding many physiological, bio-
chemical processes and different pathways involved in the development of cancer
[ 10 ]. These in vivo models mimic the human disease closely, and allow testing new
therapies and target orientated drug screening [ 11 ]. In spite of these animal models
providing significant information regarding drug efficacy, several factors should be
considered while inferring mouse data to the clinical testing [ 10 ]. Monitoring lifes-
pan of animals and caliper-based measurements are commonly used for the response
of therapeutic efficacy and target-drug interactions in subcutaneous tumor xenograft
models [ 12 , 13 ]. However, measuring tumor size with calipers has several limita-
tions, such as, not providing the internal structure and the cellular heterogeneity of
the tumor. Furthermore, therapeutic agents having cytostatic effect, but not cyto-
toxic, may not result in decrease in tumor size, thus leading to miscalculation of the
effect of therapeutic agents [ 14 ]. Regardless, caliper measurements may not be a
good option for mouse-human myeloma models since myeloma grows in the pro-
tective bone microenvironment.
6.2.1 Murine-Human Model for Myeloma
The xenograft models of MM, in which human MM cells grow in immunocompro-
mised mice, have been beneficial in optimizing drug schedules and doses and have
undoubtedly benefited the MM patients [ 15 ]. Myeloma cell lines or primary
myeloma cells are grown within human fetal bone, implanted subcutaneously in
6 MRI & PET for Evaluation of Myeloma in SCID-hu Mice