¹¹¹In-Diethylenetriamine pentaacetic acid-single-walled nanotubes

[¹¹¹In-DTPA-SWNTs]

Background

[PubMed]

Optical fluorescence imaging is increasingly used to visualize biological functions of specific targets (1, 2). However, the intrinsic fluorescence of biomolecules poses a problem when fluorophores that absorb visible light (350–700 nm) are used. Near-infrared (NIR) fluorescence (700–1,000 nm) detection avoids the background fluorescence interference of natural biomolecules, providing a high contrast between target and background tissues. NIR fluorophores have wider dynamic range and minimal background as a result of reduced scattering compared with visible fluorescence detection. They also have high sensitivity, resulting from low infrared background, and high extinction coefficients, which provide high quantum yields. The NIR region is also compatible with solid-state optical components, such as diode lasers and silicon detectors. NIR fluorescence imaging is becoming a non-invasive alternative to radionuclide imaging in small animals.

Carbon nanotubes are made of fullerene carbon units, which respond to local dielectric changes without photo-bleaching (3, 4). They can be tuned to a range of wavelengths for NIR absorption, thus providing broad excitation profiles and high absorption coefficients. They can be coated and capped with hydrophilic materials for additional conjugation with biomolecules, such as peptides, antibodies, nucleic acids, and small organic compounds for in vitro and in vivo studies (5). Single-walled carbon nanotubes (SWNTs) have a diameter of 1–5 nm and a length of 300–1,000 nm. They have been shown to be nontoxic to cells in vitro (6). However, there have been limited studies of their in vivo toxicological and pharmacological profiles in small animals. SWNTs have been conjugated with diethylenetriamine pentaacetic acid (DTPA) and radiolabeled with ¹¹¹In to form ¹¹¹In-DTPA-SWNTs for quantitative biodistribution studies in small animals (7).

Synthesis

[PubMed]

Singh et al. (7) introduced DTPA groups to NH₂-SWNTs (0.5 mmol NH₂/g) by incubation of NH₂-SWNTs (1.4 nm in diameter and 300–1,000 nm in length) with diisopropylethylamine and DTPA dianhydride for 3 h at room temperature. DTPA-SWNTs were diluted with water and lyophilized twice. DTPA-SWNTs were complexed with ¹¹¹In-citrate for 60 min at room temperature. ¹¹¹In-DTPA-SWNTs were used without further purification. ¹¹¹In-DTPA-SWNTs-3 contained 0.5 mmol/g DTPA with one ¹¹¹In ion per ~70,000 DTPA, whereas ¹¹¹In-DTPA-SWNTs-5 contained 0.3 mmol/g DTPA groups with one ¹¹¹In ion per ~42,000 DTPA. The specific activity of both tracers was ~12.3 MBq/mg (~0.33 mCi/mg)

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

Yehia et al. (8) performed transmission electron microscopy (TEM) and confocal Raman spectroscopy using human HeLa cells after incubation with SWNTs for up to 60 h at 37°C. SWNTs were taken up by HeLa cells in a time-dependent manner as determined with confocal Raman spectroscopy. TEM revealed that SWNTs were found in intracellular vacuoles but not in the nucleus. SWNTs did not affect the growth rates of HeLa cells.

Animal Studies

Human Studies

[PubMed]

No publication is currently available.