99mTc-N2S2-Tat (49-57)-bombesin internalized in nuclei of prostate and breast cancer cells

Abstract

The hybrid radiopharmaceutical could be potentially useful as a therapeutic agent for prostate and breast cancers.

Radiolabeled Nanoparticles for Molecular Imaging

“…99m Tc internalized in cancer cell nuclei acts as an effective system of targeted radiotherapy because of the Auger and internal conversion electron emissions near DNA. The HIV Tat(49-57) is a cell penetrating peptide that reaches DNA (Santos-Cuevas et al, 2011). Therefore, 99m Tc-labeled gold nanoparticles (5nm) prepared by the methods previously described (Ocampo-Garcia et al, 2011b;Morales-Avila et al, 2011) and conjugated to the HIV Tat(49-57) peptide, could potentially be a multifunctional system with properties suitable for targeted radionuclide therapy.…”

Radiolabelled nanoparticles: novel classification of radiopharmaceuticals for molecular imaging of cancer

“…Targets of bombesin analogues are limited to cell membrane and cytoplasm, whereas the peptide sequence TAT (49)(50)(51)(52)(53)(54)(55)(56)(57) promotes their internalization and routing in to the cell nucleus. Santos-Cuevas et al [84] demonstrated that the 99m Tc-N2S2-Tat (49-57)-Lys3-bombesin ( 99m Tc-Tat-BN) peptide is highly internalized in nuclei of breast and prostate cancer cells. At a single-cell level, short-range charged particles, such as IC electrons and Auger electrons ( 99m Tc-HYNIC-TOC), impart a dense ionizing energy deposition pattern associated with increased radiobiological effectiveness, one characteristic that becomes important when a nanoparticle is capable of reaching the nucleus.…”

Targeting the Erythrocytic and Liver Stages of Malaria Parasites with s‐Triazine‐Based Hybrids

“…An example for this approach is a 99m Tc‐labeled heterobivalent system of bombesin and the Tat sequence, serving as a cell‐penetrating peptide: [ 99m Tc]N2S2–Tat (49–57) –BBN 27. In in vitro studies, this compound showed greater uptake and internalization into three different tumor cell lines than [ 99m Tc]EDDA/HYNIC–Lys–BBN (EDDA=ethylenediaminediacetic acid), which was used as a reference compound,27a and also inhibited proliferation of these cells due to high cytoplasmic and nuclear localization of the compound 27b. However, in evaluating the compound in vivo, a high unspecific uptake in different organs was observed, together with an immense kidney accumulation, resulting in a tumor‐to‐kidney ratio of only 0.14 at 2 h p.i.,27a which limits diagnostic or, as proposed, therapeutic in vivo applications of this compound.…”