Synthesis of a new class radio-quantum dots for multimodality imaging and targeted therapy

Abstract

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Objectives: The goal of targeted therapeutics is to create drugs that by the specificity of their design and delivery will make them more effective in treating tumours and less toxic to healthy tissues. Nanotechnology offers the possibility of a device and a drug in one, with novel capabilities. Quantum nanocrystals are potentially more effective both in terms of selective delivery and specific retention in the target site. The nanoparticle size of the QD’s facilitates trapping within individual cells. This work has taken advantage of this to develop a new class of quantum dots synthesised at the radiotracer level and are termed “radio-quantum dots” (RQDs).

Methods: The proof of concept was tested demonstrated using the Cd-109. [109Cd]CdCl (0.2 nmol, 37MBq), stearic acid, and octadecene were placed in a flask was heated to 200oC to obtain a colourless clear solution. After this solution was cooled to room temperature, octadecylamine and trioctylphosphine oxide were added into the flask. this system was reheated to 280 C. At this temperature, a selenium solution was quickly injected. The growth temperature was then reduced to 250oC. The RQD’s were then coated with ZnS in order to increase there emission properties and rendered water soluble by coating with mercapto-succinic acid. The RQD’s were analysed using UV-vis, fluorescence spectroscopy, TEM and gamma ray spectroscopy

Results: Typically this reaction generated [109Cd]CdSe nanocrystals of about 2-4 nm in size based on measurements taken from the TEM. This generated a range of fluorescence emission spectra which varied from 480nm for the 2 nm dots to 620nm for 4nm dots. When compared with quantum dots manufactured using conventional methods involving stable cadmium isotopes there was no difference in either emission or absorption properties. However, gamma spectroscopy analysis of the RQD’s indicated better than 90% of the radioactivity was retained within the quantum dot crystal.

Conclusions: We now propose to develop a new class of quantum dots (RQDs) synthesized at tracer level from radioisotopes of the same elements as those used in conventional quantum dots. The development of these at the tracer level will facilitate the use of tracer quantities for high sensitivity molecular imaging. This could be accomplished by the synthesis of inorganic radionuclides for SPECT, PET, MRI imaging as well as targeted radionuclide therapy. Synthesis at the tracer level will also allow us to explore the potential of these inorganic metals as therapeutic agents when specifically targeted and retained within cells. Finally, the development of these beacons at the nano-molar level overcomes a major toxicity issue associated with the toxic levels of these elements in conventional quantum dots synthesis.