F-18-Labeled cyclen-Zn(II) complexes for in vivo imaging of apoptosis

Objectives Apoptosis, a form of programmed cell death, is an integral regulating process in multicellular organisms. It plays important roles not only in normal tissue homeostasis but also in a variety of medical disorders including cerebral stroke, myocardial infarction and cancer. Thus imaging of apoptosis is crucial for diagnosis and monitoring the course and treatment efficacy of such diseases. Nevertheless, there are only few substances in recent research that seem to be promising for in vivo appliance. Here we present the development of a new zinc-cyclen-complex in the respect of small molecule in vivo imaging of apoptosis.

Methods Based on work of Lakshmi and Hanshaw et al. we first synthesized a fluorescein labeled cyclen-Zn(II)-complex. This complex was tested in flow cytometry measurements on apoptotic Jurkat cells. Results were compared to Annexin V-Alexa Fluor treated cells. After the fluorescein complex had proved to be successful in labeling apoptotic cells quantitatively a ¹⁸F-complex was developed in the purpose of PET imaging.

Results The boc-protected precursor was labeled in two steps using ¹⁸F-ethyltosylate. The ¹⁸F-product was obtained in high purity and good yields. The ligand showed high stability under various conditions. Organ distribution and PET-imaging will be used to determine the in vivo applicability of our cyclen complex.

Conclusions The ¹⁸F-cyclen-complex is readily accessible via a straightforward synthesis and labeling procedure. Based on our results the Zn(II) cyclen complex may overcome present apoptosis detection problems and be developed into a powerful imaging agent.