Nanoplatform for Positron Emission Tomography (PET); GOPIKRISHNA.J- 08NMS014 IInd M TECH - ACNS Early cancer detection using positron emission tomography is continues to be one of the major weapon in the arsenal of modern medicine in its war on cancer. The importance of an early screening system for cancer such as PET can be understood in the light of latest statistics from NIC, according to NIC estimates about 30-35% of caner deaths can be avoided by fruitful early detection.1 PET is a functional imaging system which detects the abnormalities in metabolism of tumors thus leading to their identification. The following image illustrates various imaging methods correlated to the parameters being measured.
Because of the high metabolic activity of malignant cells, PET imaging with the glucose analog 18F-deoxyglucose (FDG) has become a very promising test for the detection of primary tumors and metastatic lesions. The highly sensitive PET scan detects the metabolic signal of actively growing cancer cells in the body and the CT scan provides a detailed picture of the internal anatomy that reveals the location, size and shape of abnormal cancerous growths PET images begin with an injection of FDG an analog of glucose that is tagged to the radionuclide F18. Metabolically active organs or tumors consume sugar at high rates, and as the tagged sugar starts to decay, it emits positrons. These positrons then collide with electrons, giving off gamma rays, and a computer converts the gamma rays into images. These images indicate metabolic "hot spots," often indicating rapidly growing tumors because cancerous cells generally consume more sugar/energy than other organs or tumors2.
Nanoplatform for the targeted delivery of Radioprobes and tumor therapy Nanoparticles can be engineered as nanoplatforms for effective and targeted delivery of drugs and imaging labels by overcoming the many biological, biophysical, and biomedical barriers. Several barriers exist for in vivo applications in preclinical animal models and eventually clinical translation of nanotechnology, among which are the biocompatibility, in vivo kinetics, targeting efficacy, acute and chronic toxicity, and cost-effectiveness The pharmacokinetics, tumor uptake, and therapeutic efficacy of an 111In labeled chimeric L6 (ChL6) monoclonal antibody-linked iron oxide nanoparticle was studied in athymic mice bearing human breast cancer HBT 3477 tumors.111In-labeled ChL6 was conjugated to carboxylated polyethylene glycol (PEG) on dextran-coated iron oxide nanoparticles (_20 nm in diameter), with one to two ChL6 antibodies per nanoparticle. It was proposed that the time this nanoparticle remained in the circulation was long enough to provide ample opportunity for it to exit the blood vessels and access the cancer cells. Inductively heating the nanoparticle with an externally applied alternating magnetic field (AMF) caused tumor necrosis at 24 h after AMF therapy. In a follow-up study, different doses of AMF were delivered at 72 h after nanoparticle injection. PET imaging was carried out to quantify the nanoparticle uptake in the tumor, which was about 14 percentage injected dose per gram at 48 h post-injection. Delay in tumor growth occurred after AMF treatment3.
Figure showing the attachment of nano- radio conjugates to HBT 3477 tumors.
Nanoplatform for PET γ detectors. A PET detector is basically is a scintillation crystal, which emits visible photons on contact with high energy radiation like gamma rays. Two gamma rays produced by electron- positron annihilation reaction is converted in to visible light by gamma ray cameras, which intern converted in to electrical data.
The process of light emission in a scintillation crystal can be divided in to three steps, conversion, transport and luminescence During the conversion an interaction of a high-energy photon with the lattice of the scintillator material occurs electron-hole pairs are created and thermalized. In the transport process , electrons and holes (possibly also excitons) migrate through the material, possible trapping at defects occurs, energy losses are probable due to nonradiative recombination etc. The final stage, luminescence, consists in trapping the charge carriers at the luminescence centre and in their subsequent radi ative recombination. In a particular group of material the light generation occurs in radiative transition between the valence and first core bands, these are so called crossluminescence scintillators4.
Figure showing the mechanism of scintillation. A large number of studies are peogressing on the photonics of nanocrystals nowdays, sinc escientillation is depended upon the bandwith of the materials great deals of manupultions xcan be done in nanolevel. Recently a silicon based hybrid scientilation matrial was developed towards this goal. The newly developed hybrid material showed enhanced optical properties on comparison with the conventional detectors.5
Experimental demonstration of improvement in the spectral response of a Si detector when hybridized with a nanocrystal scintillator (using red CdSe/ZnS nanocrystals)
It has also been demonstrated that on using the nanocrystal based detecters noice can be redused leading to better quality of scan6.
Nanoplatform for collimators. Collimators are the slits used to reduce noise by preventing the scattered gamma rays from hitting the detectors. A metanalysis of deferent kinds of collimators done by a group of scientists in University of Utah, have demonstrated the importance of size dependence of collimators over its performance. Hence nanolithography certainly have a great role to play in the development of collimators like devises.6. The study found that the ratios of singles to trues were decreasing with a decrease in the collimator thickness and with an increase in collimator length. Hence long nanobars can be an ideal choice for these collimators.
References; 1. The journal of nuclear medicine • 48 •.1 (Suppl) • 2007.4S-18S 2. MEDICAMUNDI. 46 .1. 2002.2-8 3. Clin Cancer Res .11. 1, 2005 .7087-7092. 4. Journal of Ceramic Processing Research. 5, 2, 2004., 101~105. 5. OPTICS EXPRESS 15,. 3 , 2007.1128-1134 6. IEEE Trans. Nucl. Sci., 47,2000. 1051, 2000.