The correlation of serum protein association and cellular uptake with lipophilicity and polarity of the backbone substituents of the technetium-99m-amine-oxime chelates
✍ Scribed by Li Li; Yong Xu; Zifen Su
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- French
- Weight
- 113 KB
- Volume
- 50
- Category
- Article
- ISSN
- 0022-2135
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
Detection of tumor hypoxia is of importance because hypoxic cancer cells can resist radiation therapy and also induce molecules to help them surviving and metastasizing. Our previous study has reported the development of technetium‐99m labeled amine‐oxime compounds containing 2‐nitroimidazoles to target hypoxic cells. In order to develop new generation of ^99m^Tc, ^64^Cu, and ^67^Cu based amine‐oxime chelates with improved selectivity on tumor hypoxia in the future, it is important to understand the correlation of some structural parameters such as lipophilicity and polarity of the backbone ‐constituents of a radiochelate with its serum protein binding potential and cellular‐uptake‐level. The correlation is investigated in this work by using five ^99m^Tc‐amine‐oxime chelates containing 2‐NI group and another five containing aniline group (as control). The results indicate that the level of protein‐and cellular‐binding of a radiochelate increased with their lipophilicity which generally correlates with the lengthening of the alkyl chains on the backbone of the radiochelates. The greater lipophilicity of a radiochelate, the higher percentage it bound to serum proteins and cellular membrane. Our study also indicates that, in addition to lipophilicity, polarity of the constituents is also an important factor of determining the levels of serum protein binding and cellular accumulation of a radiochelate. Copyright © 2007 John Wiley & Sons, Ltd.