Table of Contents
Noninvasive Functional Imagingdrug delivery to target (kinetics, PK) assess modulators of delivery (transport) drug impact on target (dynamics, PD) inhibit enzyme, process, receptor angiogenesis, blood flow, energetics
Imaging Proliferation (DNA Synthesis) Thymidine or Analogs dTMP ? ? DNA (TK) ? dThd1. Direct use of circulating dThd for DNA synthesis provides a potential probe.2. In the lab, when 3H-dThd added, it’s interpreted as “labeling-index” or “proliferation marker.” 3. Can also use BUDR, IUDR, FIAU, FMAU.
Thymidine as a Proliferation Marker Drawback:dThd ?Thy ? ? bicarbonate; CO2Rapidly & extensively catabolized (radiolabeled products circulating as “background noise”)Practical Alternatives to dThd: -- Must Block Catabolism -- While Retaining Anabolism
CELL CULTURE DATA SHOWS: dTMP ? ? DNA (TK) ? dThd FMAUMP ? ? DNA (TK)? FMAU FMAU readily enters cellsFMAU phosphorylated by TK to FMAUMPFMAUMP incorporated into DNAExtract DNA,digest,measure FMAU by HPLC
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