599labeled, it is injected into the patient. The positrons that are emitted from the isotopes
then interact locally with negatively charged electrons and emit what is called anni-
hilating radiation. This radiation is detected by an external ring of detectors. It is the
timing and position of the detection that indicates the position of the molecule in
time and space. Images can then be constructed tomographically, and regional time
activities can be derived. The kinetic data produced provide information about the
biological activity of the molecule. Molecular imaging provides in vivo information
in contrast to the in vitro diagnostics. Moreover, it provides a direct method for the
study of the effect of a drug in the human body. Personalized medicine will involve
the integration of in vitro genotyping and in vivo phenotyping techniques.
Molecular Imaging for Personalized Drug Development in Oncology
For decades anatomic imaging with CT or MTI has facilitated drug development in
medical oncology by providing quantifi able and objective evidence of response to
cancer therapy. In recent years metabolic imaging with 18Ffl uorodeoxyglucose-
PET has added an important component to the oncologist’s armamentarium for ear-
lier detection of response that is now widely used and appreciated. These modalities
along with ultrasound and optical imaging (bioluminescence, fl uorescence, near-
infrared imaging, multispectral imaging) have become used increasingly in pre-
clinical studies in animal models to document the effects of genetic alterations on
cancer progression or metastases, the detection of minimal residual disease, and
response to various therapeutics including radiation, chemotherapy, or biologic
agents. The fi eld of molecular imaging offers potential to deliver a variety of probes
that can image noninvasively drug targets, drug distribution, cancer gene expres-
sion, cell surface receptor or oncoprotein levels, and biomarker predictors of prog-
nosis, therapeutic response, or failure. Some applications are best suited to accelerate
preclinical anticancer drug development, whereas other technologies may be
directly transferable to the clinic. Efforts are underway to apply noninvasive in vivo
imaging to specifi c preclinical or clinical problems to accelerate progress in the
fi eld. By enabling better patient selection and treatment monitoring strategies,
molecular imaging will likely reduce the future cost of drug development.
As anticancer strategies become more directed towards a defi ned molecular tar-
get, we need information that is relevant to humans about whether the molecular
target is expressed, the selectivity and binding of the compound for that target, and
the effects of such an interaction. The following is an example of the use of molecu-
lar imaging in drug discovery for cancer.
p53 defi ciency is common in almost all human tumors and contributes to an
aggressive chemo- or radiotherapy-resistant phenotype, therefore providing a target
for drug development. Molecular targeting to restore wild-type p53 activity has
been attempted in drug development and has led to the identifi cation of CP-31398,
PRIMA1, and the Nutlins. The use of noninvasive bioluminescence imaging has
been demonstrated in a high-throughput cell-based screen of small molecules that
activate p53 responses and cell death in human tumor cells carrying a mutant p53
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