One-Pot Radiosynthesis and Biological Evaluation of a Caspase-3 Selective 5-[123,125I]iodo-1,2,3-triazole derived Isatin SPECT Tracer

Sci Rep. 2019 Dec 17;9(1):19299. doi: 10.1038/s41598-019-55992-0.

Abstract

Induction of apoptosis is often necessary for successful cancer therapy, and the non-invasive monitoring of apoptosis post-therapy could assist in clinical decision making. Isatins are a class of compounds that target activated caspase-3 during apoptosis. Here we report the synthesis of the 5-iodo-1,2,3-triazole (FITI) analog of the PET tracer [18F]ICMT11 as a candidate tracer for imaging of apoptosis with SPECT, as well as PET. Labelling with radioiodine (123,125I) was achieved in 55 ± 12% radiochemical yield through a chelator-accelerated one-pot cycloaddition reaction mediated by copper(I) catalysis. The caspase-3 binding affinity and selectivity of FITI compares favourably to that of [18F]ICMT11 (Ki = 6.1 ± 0.9 nM and 12.4 ± 4.7 nM, respectively). In biodistribution studies, etoposide-induced cell death in a SW1222 xenograft model resulted in a 2-fold increase in tumour uptake of the tracer. However, the tumour uptake was too low to allow in vivo imaging of apoptosis with SPECT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Caspase 3 / chemistry
  • Caspase 3 / genetics
  • Caspase 3 / isolation & purification*
  • Cell Line, Tumor
  • Copper / chemistry
  • Fluorine Radioisotopes / chemistry
  • Fluorine Radioisotopes / pharmacology
  • Heterografts
  • Humans
  • Iodine Radioisotopes / chemistry
  • Iodine Radioisotopes / pharmacology*
  • Isatin / chemical synthesis
  • Isatin / pharmacology
  • Mice
  • Neoplasms / diagnostic imaging*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacology
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon / methods
  • Triazoles / chemical synthesis
  • Triazoles / pharmacology

Substances

  • Fluorine Radioisotopes
  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • Triazoles
  • Copper
  • Isatin
  • Caspase 3