The caCORE Software Development Kit: Streamlining construction of interoperable biomedical information services

BACKGROUND: Robust, programmatically accessible biomedical information services that syntactically and semantically interoperate with other resources are challenging to construct. Such systems require the adoption of common information models, data representations and terminology standards as well as documented application programming interfaces (APIs). The National Cancer Institute (NCI) developed the cancer common ontologic representation environment (caCORE) to provide the infrastructure necessary to achieve interoperability across the systems it develops or sponsors. The caCORE Software Development Kit (SDK) was designed to provide developers both within and outside the NCI with the tools needed to construct such interoperable software systems. RESULTS: The caCORE SDK requires a Unified Modeling Language (UML) tool to begin the development workflow with the construction of a domain information model in the form of a UML Class Diagram. Models are annotated with concepts and definitions from a description logic terminology source using the Semantic Connector component. The annotated model is registered in the Cancer Data Standards Repository (caDSR) using the UML Loader component. System software is automatically generated using the Codegen component, which produces middleware that runs on an application server. The caCORE SDK was initially tested and validated using a seven-class UML model, and has been used to generate the caCORE production system, which includes models with dozens of classes. The deployed system supports access through object-oriented APIs with consistent syntax for retrieval of any type of data object across all classes in the original UML model. The caCORE SDK is currently being used by several development teams, including by participants in the cancer biomedical informatics grid (caBIG) program, to create compatible data services. caBIG compatibility standards are based upon caCORE resources, and thus the caCORE SDK has emerged as a key enabling technology for caBIG. CONCLUSION: The caCORE SDK substantially lowers the barrier to implementing systems that are syntactically and semantically interoperable by providing workflow and automation tools that standardize and expedite modeling, development, and deployment. It has gained acceptance among developers in the caBIG program, and is expected to provide a common mechanism for creating data service nodes on the data grid that is under development

Synthesis and characterization of 123I-CMICE-013: A potential SPECT myocardial perfusion imaging agent

Coronary artery disease (CAD) is a major cause of death in Canada and the United States. Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a useful diagnostic test in the management of patients with CAD. The widely used SPECT MPI agents, 99mTc sestamibi and 99mTc tetrofosmin, exhibit less than ideal pharmacokinetic properties with decreasing uptake with higher flows. 123I has a similar energy as 99mTc, an ideal half life, and is readily available from cyclotrons. The objective of this study was to develop an 123I labeled MPI agent based on rotenone, a mitochondrial complex I inhibitor, as an alternative to currently available SPECT MPI agents. Methods: 123I-CMICE-013 was synthesized by radiolabeling rotenone with 123I in trifluoroacetic acid (TFA) with iodogen as the oxidizing agent at 60 C for 45 min, followed by RP-HPLC purification. The product was formulated in 5% EtOH in 10 mM NaOAc pH 6.5. The inactive analog 127I-CMICE-013 was isolated and characterized by NMR and mass spectrometry, and the structure determined. Micro-SPECT imaging studies were carried out in normal and infarcted rats. Biodistribution studies were performed in normal rats at 2 h (n = 6) and 24 h (n = 8) post injection (p.i.). Results: 123I-CMICE-013 was isolated with >95% radiochemical purity and high specific activity (14.8-111 GBq/μmol; 400-3000 mCi/μmol). Structural analysis showed that rotenone was iodinated at 7′-position, with removal of the 6′,7′-double bond, and addition of a hydroxy group at 6′-position. MicroSPECT images in normal rats demonstrated homogeneous and sustained myocardial uptake with minimal interference from lung and liver. Absent myocardial perfusion was clearly identified in rats with permanent left coronary artery ligation and ischemia-reperfusion injury. In vivo biodistribution studies in normal rats at 2 h p.i. showed significan