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Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

ABSTRACT: Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared - non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.

SUBMITTER: Zhang L

PROVIDER: S-EPMC4857130 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

Zhang Liang L Bhatnagar Sumit S Deschenes Emily E Thurber Greg M GM

Scientific reports 20160505

Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specif ...[more]

PMID: 27147293

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Dataset Information

Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

Publications

Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

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