Novel radiopharmaceutical (Technetium-99m)-(DOTA-NHS-ester)-Methionine as a SPECT-CT tumor imaging agent

Eur J Pharm Sci. 2020 Jan 1:141:105112. doi: 10.1016/j.ejps.2019.105112. Epub 2019 Oct 17.

Abstract

Breast cancer is the most common type of cancer in women worldwide. There have been many efforts for early breast cancer detection and among them molecular imaging have been extremely of high importance. Single-photon emission computed tomography (SPECT/CT) is a kind of imaging technique able to reveal crucial information with using radiopharmaceuticals. In this study, Technetium-99m-(DOTA-NHS-ester)-Methionine radiopharmaceutical was synthesized. Between 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid mono-N-hydroxysuccinimide ester (DOTA-HNS ester) (MACROCYCLICS, DOTA-NHS ester, Plano, Texas, USA) and methionine(marker) were conjugated. The DOTA-HNS ester-Methionine was labeled with Technetium-99m (Inter-Medical, Technetium-99m, Bergamo, Italy). The synthesized radiopharmaceutical was used in SPECT/CT imaging for breast cancer diagnosis. For radiopharmaceutical evaluation, MTT assay for cellular toxicity, biodistribution, cellular uptake and radiochemical purity were employed.Technetium-99m-(DOTA-NHS-ester)-Methionine radiochemical had less cellular toxicity in human embryonic kidney cells 293 cell line (HEK293). Cellular uptake was indicated higher percent with use of Methionine as a marker, and radiochemical purity was high. Based on the results Technetium-99m-(DOTA-NHS-ester)-Methionine radiochem may be a better option for early detection of breast cancer. Further study is recommended to confirm these findings in clinical practice.

Keywords: 99mTc; Biodistribution; DOTA-NHS; Imaging; Methionine; SPECT.

MeSH terms

  • Animals
  • Biological Transport
  • Cell Survival / drug effects
  • Contrast Media / administration & dosage*
  • Contrast Media / pharmacokinetics
  • Esters
  • HEK293 Cells
  • Humans
  • MCF-7 Cells
  • Male
  • Methionine / administration & dosage*
  • Methionine / pharmacokinetics
  • Mice
  • Neoplasms / metabolism
  • Radiopharmaceuticals / administration & dosage*
  • Radiopharmaceuticals / pharmacokinetics
  • Succinimides / administration & dosage*
  • Succinimides / pharmacokinetics
  • Technetium / administration & dosage*
  • Technetium / pharmacokinetics
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Contrast Media
  • DOTA-NHS
  • Esters
  • Radiopharmaceuticals
  • Succinimides
  • Technetium
  • Methionine