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Journal of Diagnostic Imaging in Therapy. 2014; 1(1): 103-109

Eckelman

Commentary
Keywords: radionuclide therapy, phenotype screening, molecular target screening, biomarkers
Although targeted radionuclide therapy is perhaps the greatest opportunity to affect patient care, it has
not been the major focus of Nuclear Medicine research in spite of the unparalleled early success of
[131I]iodide in treating thyroid abnormalities [1,2]. But this seems to be changing slowly [3].
Diagnostic Nuclear Medicine, on the other hand, is still primarily dependent on those
radiopharmaceuticals (radiolabeled with Tc-99m) that monitor high capacity sites, e.g., for myocardial
and cerebral blood flow, glomerular filtration, phagocytosis, hepatocyte clearance, and bone adsorption
for staging disease or the effect of treatment [4].
The pharmaceutical industry has a similar situation in that drugs were based primarily on phenotypic
screening in the pre-genomic era and molecular targeted screening in the post-genomic era. Phenotypic
screening uses a model of the disease and using high throughput screening, chooses the most effective
drug in that model as the lead candidate. The molecular target does not need to be known and in fact,
multiple targets and pathways may be involved. The molecular targeting approach uses a single target
chosen from studies of variant genes [5]. An example of phenotypic screening in radiopharmaceuticals
would be evaluating various Tc-99m chelates as ideal tracers of glomerular filtration in animal models
of renal function. An example of a targeted molecular probe is radiolabeled meta-iodobenzyl guanidine
(MIBG).
Based on the various approaches to linking genetic variants to specific diseases, it is clear that the
number of genetic variants for complex diseases is most often large. For example, genome-wide
association meta-analyses has confirmed the involvement of multiple variants in prostate cancer, breast
cancer, diabetes and schizophrenia [6]. To further complicate the choice of a single target, there are
several post-genomic alterations in the process of developing a potential drug target. The various
‘omics’ such as transcriptomics, epigenetics, miRNA, proteomics, phosphoproteomics and
metabolomics introduce further variants to the molecule target for external imaging [7].
As a result, next-generation genomic sequencers, not nuclear imaging in vivo, are best for identifying
and monitoring variant genes involved in a particular complex disease in order to personalize medicine
for the sampled tumor [8]. Choosing a target for a drug or an imaging agent is a more difficult
challenge for targeted imaging. Nuclear Imaging, especially, is limited to one or two targets given
patient tolerance and absorbed radiation dose.
Why targeted radionuclide therapy for oncology?
At present, there may be applications for certain infections [9], but not in either neurology, psychiatry
or cardiology. One advantage of radionuclide therapy over targeted chemotherapy is the target does not
have to be a key step in the biochemical pathway of the tumor. Rather, the criteria are a highly
ISSN: 2057-3782 (Online)
http://dx.doi.org/10.17229/jdit.2014-1110-007

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