Evaluation of Tc-99 m Labeled Dimeric GX1 Peptides for Imaging of Colorectal Cancer Vasculature.

PURPOSE: This study aimed to evaluate the potential of PEGylated dimeric GX1 peptide as a radiotracer for imaging of colorectal cancer vasculature in a LoVo tumor xenografted mouse model. PROCEDURES: The [(99m)Tc]PEG-(GX1)2 peptide was synthesized and identified. Confocal immunofluorescence analysis, receptor binding assay, and competitive inhibition assay were performed to evaluate the binding specificity and the receptor binding affinity of PEG-(GX1)2 to Co-human umbilical vein endothelial cells (HUVECs). Single photon emission computed tomography imaging and biodistribution were performed to evaluate the targeting ability of PEG-(GX1)2 to colorectal cancer. RESULTS: The studies in vitro suggested that PEG-(GX1)2 co-localized with Factor VIII in the perinuclear cytoplasm of Co-HUVECs and bound specifically to Co-HUVECs with a high affinity. The studies in vivo demonstrated that the targeting efficacy of PEG-(GX1)2 was superior to GX1. CONCLUSIONS: PEGylation improved the affinity and the targeting ability of the GX1 peptide. PEG-(GX1)2 is a more promising probe for imaging of colorectal vasculature than GX1.

Targeted radiotherapy with tumor vascular homing trimeric GEBP11 peptide evaluated by multimodality imaging for gastric cancer.

Targeted radiopharmaceutical is an effective treatment for solid tumors. By labeling with radionuclides, targeting peptide could achieve both noninvasive diagnosis and targeted radionuclide therapy. In order to evaluate the potential applicability of GEBP11 peptides in diagnosis and radiotherapy of gastric cancer, in this study, iodine 131 labeled GEBP11 peptides, including a novel bifid PEGlylated GEBP11 trimer and its corresponding monomer, were developed. The clinical potential of GEBP11 peptides, such as tumor binding affinity and antitumor efficacy was demonstrated and assessed with multimodality imaging methods. Cerenkov and SPECT imaging showed higher tumor uptake for (131)I-2PEG-(GEBP11)3 (P<0.05, day 1; P<0.01, day 2; vs. monomer). Biodistribution studies indicated higher tumor accumulation and better T/NT of (131)I-2PEG-(GEBP11)3. Bioluminescence imaging exhibited a significant tumor growth suppression in (131)I-2PEG-(GEBP11)3 treated group (P<0.001 vs. control; P<0.01 vs. monomer). After treatment with (131)I-2PEG-(GEBP11)3, the tumor volume and vasculature decreased significantly, and the survival time was prolonged to 75.5days. Meanwhile, no significant hepatic or renal toxicity was observed with (131)I-2PEG-(GEBP11)3 administered. In conclusion, (131)I-2PEG-(GEBP11)3 could be a promising candidate for peptide-based targeting therapy of gastric cancer. 2PEG-(GEBP11)3 might be a potential drug delivery vehicle for the antiangiogenic therapy of gastric cancer.

A novel tetrafunctional reagent for simultaneous intramolecular and intermolecular cross-linking of bovine hemoglobin.

A novel tetrafunctional reagent, alpha,gamma,alpha',gamma'-tetra-succinimidyl-hexanediamide-di-glutamate ester (HDG(OSu)(4)), was successfully synthesized, and a well-defined cross-linked bovine hemoglobin (mainly 128 kDa) was prepared with this reagent. Due to the spatial structure of this cross-linking reagent, the intramolecular and intermolecular cross-linking of bovine hemoglobin was formed simultaneously in one reaction. Although the cross-linked bovine hemoglobin showed a slight decrease in half-saturated O(2) pressure value (P(50), from 28.1 mm Hg to 21.7 mm Hg) and Hill coefficient (from 2.5 to 2), due to the cross-linkage, it still performed well for O(2) delivery.

A novel cross-linking reagent for bovine hemoglobin modification.

A novel cross-linking reagent, methoxypolyethelene glycol-glutamic acid, was synthesized and used to modify bovine hemoglobin. Bis-tetrameric hemoglobin with moderate affinity for O2 was obtained under the controlled reaction conditions.