title: The use of the fusion protein RGD-HSA-TIMP2 as a tumor targeting imaging probe for SPECT and PET.
abstract: The human serum albumin tissue inhibitor of metalloproteinase 2 (HSA-TIMP2) is known to possess antitumor activity, which has been attributed to its ability to inhibit endothelial cell proliferation by binding to integrin receptors. In this study, a fusion protein, cyclic arginine-glycine-aspartate (RGD)-HSA-TIMP2, formed by conjugating HSA-TIMP2 with a RGD peptide, and its (123)I- and (68)Ga-labeled compounds, were synthesized and evaluated with in vivo tumor imaging using single photon emission computed tomography (SPECT) and positron emission tomography (PET). RGD-HSA-TIMP2 was synthesized by covalent bonding of the RGD peptide to the side chain amino groups of HSA-TIMP2 from a two-step reaction involving from activation with N-succinimidyl iodoacetate. This conjugation improved the anticancer effect of HSA-TIMP2 in cancer cells. The (123)I- and (68)Ga-labeled fusion proteins were prepared and subsequently injected into the tail veins of mice bearing human glioblastoma cancer U87MG xenografts for SPECT and PET imaging and biodistribution studies. Tumor uptake of radioligand was high in both the PET images and in the biodistribution studies at 3 h after injection. These studies demonstrated that the new fusion protein has potential not only as an anticancer agent but also as a radioligand for the diagnosis of tumors.
authors: Division of Magnetic Resonance Research, Korea Basic Science Institute, Ochang, Chungbuk, Republic of Korea.
authors: Naeun
authors: N
authors: Choi
authors: Sung-Min
authors: SM
authors: Kim
authors: Kwan Soo
authors: KS
authors: Hong
authors: Gyunggoo
authors: G
authors: Cho
authors: Jee-Hyun
authors: JH
authors: Cho
authors: Chulhyun
authors: C
authors: Lee
authors: Eun Kyoung
authors: EK
authors: Ryu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005682:Gadolinium / Q000737:chemistry / Q000378:metabolism; D005909:Glioblastoma / Q000000981:diagnostic imaging; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D008297:Male; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012709:Serum Albumin / Q000235:genetics / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D007457:Iodine Radioisotopes; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; D019716:Tissue Inhibitor of Metalloproteinase-2; C047981:arginyl-glycyl-aspartic acid; D005682:Gadolinium