Molecular Imaging-Guided Theranostics and Personalized Medicine

Molecular imaging agents and a parallel progress in instrumentation ofimaginingtechnology have demonstrated to be effective in improving diagnosis, prognosis, planning, and monitoring of personalized medication. Molecular imaging modalities include positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), computed tomography (CT), ultrasound (US), and optical (Raman, quantum dots, bioluminescence). Among these imaging modalities, PET and SPECT agents could provide target specific information as well as function, pathway activities, and cell migration in the intact organism. Furthermore, the radiotracer could noninvasively assess diseases treatment endpoints which used to rely almost exclusively on biopsies and histopathological assays. New leads on the development of personalized theranostic (image and treat) agents would allow more accuracy in the selection of patients who may respond to treatment. 
 
Topics covered in this special issue include advances in biomarkers in preclinical drug discovery, PET/CT and SPECT/CT in disease management, image-guided therapy approach of diseases, imaging technology in drug development, and progress in instrumentation ofimagingtechnology. For instance, upregulation of transporter expressions has often been observed in tumor cells to facilitate their accelerated rates of uptake. Advances in biomarkers in transporter system-based imaging in oncology and neurological diseases such as amino acid (FL. Kong et al.), glucose (YH. Zhang et al.) and dopaminergic (LH. Shen et al.; HF. Hou et al.) transporters were reported. These biomarkers showed that specific uptake in lesions compared to clinic imaging agent. In addition, these biomarkers were capable to be labeled with theranostic isotopes for personalized medication. 
 
Most tumors have a considerable proportion of hypoxic cells that are resistant to radio/chemotherapy, with a high propensity to metastasize, and result in worse therapeutic outcome. The contribution by M. Ali et al. and H. Fuji report their newly developed 99mTc-N4-NIM and 125I-IPOS probes for tumor hypoxia. The preclinical findings showed that these biomarkers could image tumor hypoxia by SPECT. The ability to quantify tissue hypoxia would allow the physicians to select patients for additional or alternative treatment regimens that would circumvent the ominous impact of hypoxia. Along this line, L. Jiang and coworkers report the peptide based radiotracer targeting tumor angiogenesis via VEGF integrin alpha(v) beta3. J. Sims-Mourtada and co-workers report 131I-labeled derivatives of the sonic hedgehog (HH) protein for detection of cancer cells via HH receptors. Molecular imaging of cancer stem cell trafficking was reported by T. Xia and co-workers. 
 
Hybrid molecular imaging modalities (PET/CT, SPECT/CT) provide high-sensitivity functional and high resolution anatomical imaging, which are important in design personalized treatment. To avoid radiation exposure from multiple slices-CT, K. Tang and co-workers report a reduction of CT tube voltage from 120 kv to 80 kv, the radiation dose could be reduced by 32–42% without losing low-contrast detectability. F. Chao and H. Zhang report the value of using PET/CT in the staging of nonsmall cell lung cancer. Y. Hu and co-workers report the application of PET/CT in assessment of treatment outcome. The application of SPECT/CT in the differential diagnosis of bone metastasis (Y. Zhang et al.) and Parkinson's disease (L. Wang et al.) was reported. Miyake K and co-workers report the application of FDG, MET, and FLT-PET/CT for the management of gliomas. L. Yang and co-workers report the value of using myocardial contrast echocardiography quantitative analysis during adenosine stress over visual analysis before therapy in acute coronary pain. The quantitative analysis correlates well with thrombosis in myocardial infarction. 
 
In summary, molecular imaging could integrate metabolomics and chemical biology. Molecular imaging agents could characterize target expressions, understand the disease progression, prediction for drug response and toxicity, staging, grading, and micrometastasis, and support animal studies. This special issue provides a platform of efficacy of personalized medication from molecular imaging technology which may have high impact on drug discovery, delivery, and development. 
 
 
Hong Zhang 
 
Mei Tian 
 
Enzhong Li 
 
Yasuhisa Fujibayashi 
 
Lie-Hang Shen 
 
David J. Yang

guidance in the areas of targeting epigenetic abnormalities and tumor microenvironment in overcoming resistance in cancers. The use of image-guided technologies to select patient for personalized therapy and to monitor therapeutic outcomes is the focus of this special issue. For instance, mutations in the kinase domain of epidermal growth factor receptor (EGFR) have been associated with clinical responsiveness using tyrosine kinase inhibitors for nonsmall cell lung cancer (NSCLC  Topics covered in this special issue are advances in molecular imaging both in radioactive and nonradioactive applications in preclinical drug discovery, drug development, drug delivery, pharmacokinetics and pharmacodynamics, and differential diagnosis. For nonradioactive molecular imaging technology, F. C. Wong et al. reported photo affinity labeling using tissue-penetrating radiation (X-ray or gamma rays), which could overcome the tissue attenuation and irreversibly label membrane receptor proteins. They described that X-ray and gamma rays could induce affinity labeling of membrane receptors in a manner similar to UV with photo reactive ligands of the dopamine transporters, D2 dopamine receptors, and peripheral benzodiazepine receptors. P.-C. Chu et al.
reported that the brain tumor conditions on the distribution and dynamics of small molecule leakage into targeted regions of the brain could be influenced by focused ultrasound (FUS)-BBB opening. Their findings indicated that FUS-BBB opening might have the most significant permeabilityenhancing effect on tumor peripheral. Their report provides useful information toward designing an optimized FUS-BBB opening strategy to deliver small-molecule therapeutic agents into brain tumors.
MRI has been proven to be a valuable tool to provide important information facilitating individualized imageguided treatment and personalized management for cancers. J.-H. Chen and M.-Y. Su reviewed the use of different MR imaging methods, including dynamic contrast-enhanced MRI proton MR spectroscopy, and diffusion-weighted MRI, to monitor and evaluate the treatment response. They also described how the changes of parameters measured at an early time after initiation of a drug regimen could predict final treatment outcome. H.-W. Kao et al. also reviewed advanced MR imaging techniques including cellularity, invasiveness, mitotic activity, angiogenesis, and necrosis in gliomas. Molecular imaging with MRI also permits mapping and measuring the rate of physiological, biochemical, and molecular process with the use of appropriate kinetic models. For instance, T. Y. Siow et al. described their MRI findings with increased nNOS activity in brain cortex and striatum after 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. They concluded that the transient changes in hyperperfusion state in cerebral blood flow in the cortex and striatum might be an early indicator of neuronal inflammation.
T.-L. Yang et al. compared the diagnostic performance of digital breast tomosynthesis (DBT) and digital mammography (DM) for breast cancers. They concluded that adjunctive DBT provided exquisite information for mass lesion, focal asymmetry, and/or architecture distortion which could improve the diagnostic performance in mammography. Y.-C. Liu et al. reported the validation of the clinical significance of coronary artery calcium score (CACS) in predicting coronary artery disease (CAD) and cardiac events using a 64slice coronary CT angiography. They concluded that CACS was significantly correlated with CAD and cardiac events.
The emergence of flat-detector X-ray angiography in conjunction with contrast medium injection and specialized reconstruction algorithms can provide not only high-quality and high-resolution CT-like images but also functional information. This improvement in imaging technology allows quantitative assessment of intracranial hemodynamics and subsequently in the same imaging session. S.-C. Hung et al. described the recent developments in the field of flat-detector imaging and shared their experience of applying this technology in neurovascular disorders such as acute ischemic stroke, cerebral aneurysm, and steno occlusive carotid diseases.