This review aimed to arrange the concepts of a network meta-analysis (NMA) and to demonstrate the analytical process of NMA using Stata software under frequentist framework. The NMA tries to synthesize evidences for a decision making by evaluating the comparative effectiveness of more than two alternative interventions for the same condition. Before conducting a NMA, 3 major assumptions—similarity, transitivity, and consistency—should be checked. The statistical analysis consists of 5 steps. The first step is to draw a network geometry to provide an overview of the network relationship. The second step checks the assumption of consistency. The third step is to make the network forest plot or interval plot in order to illustrate the summary size of comparative effectiveness among various interventions. The fourth step calculates cumulative rankings for identifying superiority among interventions. The last step evaluates publication bias or effect modifiers for a valid inference from results. The synthesized evidences through five steps would be very useful to evidence-based decision-making in healthcare. Thus, NMA should be activated in order to guarantee the quality of healthcare system.

Current contrast agents generally have one function and can only be imaged in monochrome, therefore, the majority of imaging methods can only impart uniparametric information. A single nano-particle has the potential to be loaded with multiple payloads. Such multi-modality probes have the ability to be imaged by more than one imaging technique, which could compensate for the weakness or even combine the advantages of each individual modality. Furthermore, optical imaging using different optical probes enables us to achieve multi-color in vivo imaging, wherein multiple parameters can be read from a single image. To allow differentiation of multiple optical signals in vivo, each probe should have a close but different near infrared emission. To this end, we synthesized nano-probes with multi-modal and multi-color potential, which employed a polyamidoamine dendrimer platform linked to both radionuclides and optical probes, permitting dual-modality scintigraphic and 5-color near infrared optical lymphatic imaging using a multiple excitation spectrally-resolved fluorescence imaging technique. Keywordsdendrimer; scintigraphy; near infrared; fluorescence imaging; multiple modalities; multiple colors; lymphatic imaging No imaging modality is perfect. Each has its own distinct advantages and limitations. The simultaneous use of two or more modalities can help to overcome the limitation of each individual method and increase or improve the information obtained during an examination session. The combined use of Computed Tomography (CT) and Positron Emission Tomography (PET) is a successful example of multi-modal imaging: CT provides high resolution anatomical detail and PET provides functional information 1 . Currently they are very few examples of multi-modal imaging probes that can be detected by more than one technique: dual agents for recognition by both radionuclide and optical imaging 2,3 , or Magnetic Resonance (MR) and optical imaging 4-8 . Furthermore, the conventional imaging methods are generally monochrome and only able to detect one contrast agent at a time, limiting us to single parametric data. Single photon scintigraphy has been shown to have potential for simultaneously detecting two different imaging agents, i.e. technetium-99m and thallium-201, by energy resolution 9 . However, in this case, both the spatial and the energy resolutions were poor and did not allow for the reconstruction of a precise image from each agent. Multi-color optical imaging is simple to achieve with the technique of spectrally resolved imaging. Herein, two or more optical agents can be differentiated on the basis of their different emission spectra. Multi-color imaging is already commonplace in microscopic imaging and is beginning to be utilized for in vivo imaging 10-12 . However, in vivo imaging is essentially limited to long wavelength dyes that emit in the near-infrared (NIR) range (650-850 nm), in order to maximize depth penetration and limit the autofluorescence, background signal 13 .With this in mind we have synthe...

A target cell-specific activation strategy for improved molecular imaging of peritoneal implants has been proposed, in which fluorophores are activated only in living targeted cells. A current example of an activatable fluorophore is one that is normally self-quenched by attachment to a peptide backbone but which can be activated by specific proteases that degrade the peptide resulting in ''dequenching.'' In this study, an alternate fluorescence activation strategy is proposed whereby self-quenching avidin-rhodamine X, which has affinity for lectin on cancer cells, is activated after endocytosis and degradation within the lysosome. Using this approach in a mouse model of peritoneal ovarian metastases, we document target-specific molecular imaging of submillimeter cancer nodules with minimal contamination by background signal. Cellular internalization of receptor-ligand pairs with subsequent activation of fluorescence via dequenching provides a generalizable and highly sensitive method of detecting cancer microfoci in vivo and has practical implications for assisting surgical and endoscopic procedures. [Cancer Res 2007;67(6):2791-9]

Purpose: Epidermal growth factor receptors (EGFR) play an important role in tumorigenesis and, therefore, have become targets for new molecular therapies. Here, we use a “cocktail” of optically labeled monoclonal antibodies directed against EGFR-1 (HER1) and EGFR-2 (HER2) to distinguish tumors by their cell surface expression profiles. Experimental Design: In vivo imaging experiments were done in tumor-bearing mice following s.c. injection of A431 (overexpressing HER1), NIH3T3/HER2+ (overexpressing HER2), and Balb3T3/DsRed (non-expression control) cell lines. After tumor establishment, a cocktail of optically labeled antibodies: Cy5.5-labeled cetuximab (anti-HER1) and Cy7-labeled trastuzumab (anti-HER2) was i.v. injected. In vivo and ex vivo fluorescence imaging was done. For comparison with radionuclide imaging, experiments were undertaken using 111Indium-labeled antibodies. Additionally, a “blinded” diagnostic study was done for mice bearing one tumor type. Results: In vivo spectral fluorescent molecular imaging of 14 mice with three tumor types clearly differentiated tumors using the cocktail of optically labeled antibodies both in vivo and ex vivo. Twenty-four hours after injection, A431 and NIH3T3/HER2+ tumors were detected distinctly by their peak on Cy5.5 and Cy7 spectral images, respectively; radionuclide imaging was unable to clearly distinguish tumors at this time point. In blinded single tumor experiments, investigators were able to correctly diagnose a total of 40 tumors. Conclusion: An in vivo imaging technique using an antibody cocktail simultaneously differentiated two tumors expressing distinct EGFRs and enabled an accurate characterization of each subtype.

No abstract