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Updated: Jun 22, 2026
High-throughput Fluorometric Measurement of Potential Soil Extracellular Enzyme Activities
Published on: November 15, 2013
[Not Available]
Franziska Graf1, Lena Koehler, Torsten Kniess
1Research Center Dresden-Rossendorf, Institute of Radiopharmacy, P.O. Box 510119, 01314 Dresden, Germany.
Abstract:
The cyclin-dependent kinase (Cdk)-cyclin D/retinoblastoma (pRb)/E2F cascade, which controls the G1/S transition of cell cycle, has been found to be altered in many neoplasias. Inhibition of this pathway by using, for example, selective Cdk4 inhibitors has been suggested to be a promising approach for cancer therapy. We hypothesized that appropriately radiolabeled Cdk4 inhibitors are suitable probes for tumor imaging and may be helpful studying cell proliferation processes in vivo by positron emission tomography. Herein, we report the synthesis and biological, biochemical, and radiopharmacological characterizations of two (124)I-labeled small molecule Cdk4 inhibitors (8-cyclopentyl-6-iodo-5-methyl-2-(4-piperazin-1-yl-phenylamino)-8H-pyrido[2,3-d]-pyrimidin-7-one (CKIA) and 8-cyclopentyl-6-iodo-5-methyl-2-(5-(piperazin-1-yl)-pyridin-2-yl-amino)-8H-pyrido[2,3-d]pyrimidin-7-one (CKIB)). Our data demonstrate a defined and specific inhibition of tumor cell proliferation through CKIA and CKIB by inhibition of the Cdk4/pRb/E2F pathway emphasizing potential therapeutic benefit of CKIA and CKIB. Furthermore, radiopharmacological properties of [(124)I]CKIA and [(124)I]CKIB observed in human tumor cells are promising prerequisites for in vivo biodistribution and imaging studies.
Insights
New radiolabeled Cdk4 inhibitors, CKIA and CKIB, show promise for cancer therapy by inhibiting tumor cell proliferation. These compounds may also serve as imaging agents for studying cell growth in vivo using positron emission tomography.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Biology
Background:
- The cyclin-dependent kinase (Cdk)-cyclin D/retinoblastoma (pRb)/E2F pathway regulates cell cycle progression and is frequently altered in cancers.
- Targeting Cdk4 with selective inhibitors is a potential cancer therapeutic strategy.
Purpose of the Study:
- To synthesize and characterize novel (124)I-labeled Cdk4 inhibitors, CKIA and CKIB, for potential use in cancer imaging and therapy.
- To evaluate the efficacy of CKIA and CKIB in inhibiting tumor cell proliferation and their potential as positron emission tomography (PET) imaging agents.
Main Methods:
- Synthesis of two (124)I-labeled small molecule Cdk4 inhibitors: CKIA and CKIB.
- Biological, biochemical, and radiopharmacological characterization of CKIA and CKIB.
- Assessment of tumor cell proliferation inhibition and Cdk4/pRb/E2F pathway activity.
Main Results:
- CKIA and CKIB demonstrated defined and specific inhibition of tumor cell proliferation.
- Both compounds effectively inhibited the Cdk4/pRb/E2F pathway.
- Radiopharmacological properties of [(124)I]CKIA and [(124)I]CKIB in human tumor cells suggest suitability for in vivo imaging studies.
Conclusions:
- CKIA and CKIB show therapeutic potential by inhibiting tumor cell proliferation via the Cdk4/pRb/E2F pathway.
- [(124)I]CKIA and [(124)I]CKIB are promising candidates for in vivo tumor imaging and biodistribution studies using PET.
