Abstract IA12: Issues in the development of molecular imaging agents for cancer imaging: An observation from the MICAD editors
Authors: Shan Liang 
Published: August 2014

Abstract
Significant progress in the development of molecular imaging agents has been made during the past decade. However, the translation of the imaging agents from the laboratory to the clinic is rather slow, which can be attributed to several factors such as multidisciplinary effort requirement, stringent regulations, and economic consideration. To enhance the investigation in molecular imaging and facilitate the bench-to-bedside translation, NIH launched the Molecular Imaging and Contrast Agent Database (MICAD) in 2005, aiming to provide freely accessible online information regarding imaging probes and contrast agents. A comprehensive literature search by the MICAD editors shows that &gt;5,000 imaging agents to date have been published and characterized in vitro and in animal models of human disease, and this number increases by 300-500 new agents every year. Majority of the agents have been developed for SPECT (~36%), PET (~30%), MRI (~17%), and optical imaging (~6.5%).
On review of the published data, the MICAD editors have observed that the agents are often inconsistently or incompletely characterized, which makes it difficult to evaluate, validate, and meta-analyze the data generated from different studies of imaging agents. To address this issue, the MICAD editors have proposed several guidelines for the characterization of imaging agents developed for MRI, PET/SPECT, and optical imaging, respectively. The guidelines summarize the essential parameters that are required to characterize imaging agents from synthesis, physicochemical properties, in vitro cellular studies, to animal studies.
It is worth pointing out that it is more challenging to develop imaging agents that are specific to the tumor cells with metastatic capability. Most sensitive biomarkers are developed for the primary and advanced tumors, but few are reliable and specific for the metastatic tumor cells. It can be difficult to uncover the discordance in biological processes between the primary and disseminated tumor cells. The spatial resolution of images is sufficient to reveal whether a metastatic lesion is positive for a biomarker, but it is insufficient to delineate the spatial heterogeneity within a lesion. Furthermore, most imaging probes provide an assessment of the temporal and spatial expression distribution of a biomarker, which is not necessarily a read-out of the target activity although “smart” probes have been reported.
Because of the multidisciplinary nature of molecular imaging and the limitations of the techniques used to capture the data, there is no single set of parameters that is suitable to define the properties of the various types of imaging agents. It is essential to ensure that these agents meet certain quality control parameters at the preclinical stage so that they can be used without delay for clinical studies.
Citation Format: Liang Shan. Issues in the development of molecular imaging agents for cancer imaging: An observation from the MICAD editors. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr IA12.