Figure 68Ga-NOTA-HSA-TIMP2 and 68Ga-NOTA-RGD-HSA-TIMP2 were observed for
Figure 2 shows the interaction of radiolabelled RGDpeptide with ?v?3 integrins (Liu, 2006). Some progress in tumor-targeted imaging was made bynear-infrared fluorescence (NIRF), positron emission tomography (PET),molecular magnetic resonance imaging (MRI) single photon emission computedtomography (SPECT), or photoacoustic imaging with the aid of RGD (Haubner andWester, 2004). A fusion protein, cyclic arginine-glycine aspartate; c(RGD)-HSA-TIMP2(Human serum albumin-tissue inhibitor of metalloproteinase 2) has been preparedby Choi et al., 2011 (Choi et al., 2011).
The prepared composite was labeledwith radioactive 123I- and 68Ga, and used in the invivo tumor mapping in SPECT and PET techniques. SPECT and SPECT/CT imagesof 123I-HSA-TIMP2 and 123I -RGD-HSA-TIMP2 were observedfor 4 h after injection. The results suggested that 123I-HSA-TIMP2was not absorbed but the level of tumor uptake of 123I-HSA-RGD-TIMP2 was slightly greater in the mice bearing U87MG xenografts model.
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A chemical chelator, named as 1,4,7-triazacyclononane-1,4,7-trisacetic acid(NOTA) was used for attachment of radionuclide (68Ga) with thefusion protein. The PET and PET/CT images of 68Ga-NOTA-HSA-TIMP2 and68Ga-NOTA-RGD-HSA-TIMP2 were observed for 3 h after injection. Theresult of the study showed that the level of tumor uptake of 68Ga-NOTA-RGD-HSA-TIMP2was slightly higher than that of 68Ga-NOTA-HSA-TIMP2 .
These studiesshowed that the developed fusion protein had theranostic capability thereforethis is used as an anticancer agent as well as imaging agent for the diagnosisof tumors. Zerda et al., 2010, developed single-walled carbon nanotubesconjugated with cyclic RGD peptides which are used as contrast agent forphotoacoustic imaging of tumors. These studies suggested that these modified(targeted) nanotubes showed better photo-acoustic signal in the tumor than miceinjected with non-targeted nanotubes (Zerda et al., 2010). For effective tumortissue diagnosis Park et al.
, 2008, also developed a newer targetingmolecule i.e. Gd-DOTA-RGD helpful in MRI technique for effective tumor tissue diagnosis.This molecule showed greater R1 relaxivity (MRI signal) and quite betterspecificity for ?v?3 receptors which are present onhepatic carcinoma cells in transgenic mice (Park et al., 2008). Figure 2.Schematic presentation of the radiopharmaceuticals design.
(I) Thetargeting biomolecule (BM = RGD peptide); (II) PKM (pharmacokineticmodifying) linker; (III) Radiometal chelate (e.g., 18F-containingsynthon) (Liu, 2006). Tsiapa et al.
, 2012, also developed a newcyclic cRGDfK derivative, c(RGDfK)-(Orn)3-CGG for enhancedscintigraphic imaging. This new peptide having a polar linker ornithine (Orn)3and the Tc-chelating moiety CGG (Cys-Gly-Gly) for 99mTc-labeling, thenconjugated with nanoparticles. The complex c(RGDfK)-(Orn)3-CGG-Tcwas obtained in high radiochemical yield (>98%) and stable in vitro and exvivo. High tumor uptake (3.87 ±0.48% injected dose/g at 60 min) of peptide wasobserved which was for approximately 24 h (1.83±0.
05 % injected dose/g), thusproviding well-de?ned scintigraphic imaging (Tsiapa et al., 2013).In another study theRGD-Glu-6Ahx-RM2 (Glu: glutamic acid; 6-Ahx: 6-amino hexanoic acid; RM2:(D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2)) was conjugated with DOTA (1,4,7,10tetraazacyclododecane1,4,7,10-tetraacetic acid) bifunctional chelator (BFCA)and then radiolabeled with 111In or 177Lu. The complexwas evaluated for binding af?nity to the ?V?3 integrin orGRPr (gastrin releasing peptide receptor) in human glioblastoma U87-MG andprostate PC-3 cell lines. High tumor uptake and prolonged retention of tracer(mean of 4.41 ±0.91% injected dose/g at 24 h post-intravenous injection) wasrecorded during its biodistribution studies in tumor bearing mice.
Micro-singlephoton emission computed tomography (microSPECT) also confirmed its higherradiouptake pro?les in xenografted mice at 20 h post-injection (Reynolds etal., 2015). Liu et al., 2013 was perform the biodistribution of 99mTc-labelingof a cyclic polypeptide (RGD-4CK) in vitro on bronchio alveolar carcinoma (BAC)xenograft model.
Biodistribution studies indicated that 99mTc-RGD-4CKshowed more tumor uptake and prolongedtumor retention in xenografted nude mice. On the basis of the