Related Experiment Video

Updated: Jun 18, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Radiosynthesis and radiopharmacological evaluation of cyclin-dependent kinase 4 (Cdk4) inhibitors

Lena Koehler1, Franziska Graf, Ralf Bergmann

  • 1Institute of Radiopharmacy, Research Center Dresden-Rossendorf, Dresden, Germany.

European Journal of Medicinal Chemistry
|December 4, 2009
PubMed

Insights

Researchers developed two novel iodine-124 labeled cyclin-dependent kinase 4 (Cdk4) inhibitors for PET imaging. While showing good cell uptake, these radiotracers exhibited limited tumor visualization in preclinical models.

Area of Science:

  • Nuclear medicine
  • Radiopharmaceutical chemistry
  • Oncology

Background:

  • Tumor growth is linked to cell cycle dysregulation, particularly involving cyclin-dependent kinase (Cdk) activity.
  • Radiolabeled Cdk4 inhibitors show potential as molecular probes for positron emission tomography (PET) imaging of cell proliferation and tumors.

Purpose of the Study:

  • To design, synthesize, and evaluate two iodine-124 labeled Cdk4 inhibitors as potential radiotracers for in vivo Cdk4 imaging.
  • To assess the utility of these novel radiotracers for PET imaging of tumors.

Main Methods:

  • Synthesis and radiolabeling of Cdk4 inhibitors with iodine-124.
  • In vitro cell uptake studies using human tumor cell lines (HT-29, FaDu).
  • In vivo biodistribution studies in Wistar rats and small-animal PET imaging in a mouse FaDu xenograft model.

Main Results:

  • Radiochemical yields of up to 35% were achieved for the iodine-124 labeled inhibitors [(124)I]CKIA and [(124)I]CKIB.
  • Significant in vitro uptake was observed in HT-29 and FaDu cells.
  • Biodistribution studies revealed rapid blood clearance and liver accumulation/metabolization.
  • Small-animal PET imaging demonstrated low uptake in FaDu tumor xenografts.

Conclusions:

  • The developed [(124)I]CKIA and [(124)I]CKIB are novel Cdk4 inhibitors with good in vitro properties.
  • Despite promising cell uptake, these radiotracers showed limited efficacy for PET imaging of Cdk4 in the tested tumor models.
  • Further optimization is needed to develop effective Cdk4-targeting PET tracers for cancer imaging.

More Related Videos

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.