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Radiolabeled Peptides (radiolabeled + peptide)
Selected AbstractsPretargeted radioimmunoscintigraphy in patients with primary colorectal cancer using a bispecific anticarcinoembryonic antigen CEA X anti-di-diethylenetriaminepentaacetic acid F(ab,)2 antibody,,CANCER, Issue S4 2010Frits Aarts PhD Abstract BACKGROUND: Antibody-based imaging agents are available commercially, but their success has been limited, mainly because of low contrast and the emergence of 2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) scanning. In pretargeting, administration of the radionuclide is separated from the antibody, thereby enhancing image contrast and allowing detection at earlier time points after injection. METHODS: The authors conducted an open-label, single-arm trial that assessed a pretargeting procedure in which an anticarcinoembryonic antigen x (anti-CEA x) anti-diethylenetriaminepentaacetic acid (anti-DTPA)-indum (In) antibody was used in combination with a 111In-labeled di-DTPA peptide for the diagnostic imaging of CEA-expressing colorectal cancer. Three patients received the 111In peptide alone to investigate tumor targeting, organ distribution, and clearance of the peptide. Thereafter, 11 patients received the bispecific antibody (bsAb) (5 mg) to pretarget the tumor. After 3 to 5 days, patients were injected with 185 megabecquerels of 111In-labeled peptide to assess the optimal interval for best image quality. RESULTS: Fourteen patients with primary colorectal cancer were enrolled. One of 3 patients who received 111In peptide alone had low-level tumor uptake. In 9 of 11 other patients, tumors were observed. In 1 patient, FDG-PET,positive lymph nodes were observed clearly with pretargeted immunoscintigraphy. Peptide pharmacokinetics revealed enhanced circulating levels of 111In-labeled peptide in patients in the 3-day interval cohort compared with the other cohorts. Tumor-to-background ratios ranged from 3.5 to 6.4 in the 3-day interval group, from 5.1 to 14.2 in the 4-day interval group, and from 3.5 to 3.9 in the 5-day interval group. The best images were acquired with a 4-day interval at 24 hours after injection of the radiolabeled peptide. Grade 1 adverse events were observed in 2 patients. CONCLUSIONS: Imaging of colorectal cancer using a 2-step, pretargeting system produced the best imaging results 24 hours after peptide administration using a 4-day interval between injection of the bsAb and the peptide. Cancer 2010;116(4 suppl):1111,7. © 2010 American Cancer Society. [source] Synthesis, radiolabeling and in vitro and in vivo characterization of a technetium-99m-labeled alpha-M2 peptide as a tumor imaging agentCHEMICAL BIOLOGY & DRUG DESIGN, Issue 6 2004S.M. Okarvi Abstract:, In an effort to develop a peptide-based radiopharmaceutical for the detection of breast cancer, we have prepared an analog of ,M2 peptide, modified to incorporate an N3S chelate system. Mercaptoacetyltriglycine (MAG)3 -derivatized ,M2 peptide was prepared by solid-phase synthesis and radiolabeled with 99mTc by an exchange method. In vitro cell-binding on human breast cancer cell lines, MDA-MB-231 and MCF-7, indicated the affinity and specificity of 99mTc-MAG3 - ,M2 toward breast cancer cells. Additionally, the radiolabeled peptide showed rapid internalization into human breast cancer cells. In vivo biodistribution in mice showed that the radiolabeled peptide cleared rapidly from the blood and most non-target tissues and was excreted significantly via the kidneys. Uptake of 99mTc-MAG3 - ,M2 in the tumor was moderate. The radiochemical and in vitro and in vivo characterization indicates that the radiolabeled peptide has certain favorable properties and it might be a useful radiopharmaceutical for the detection of breast cancer in vivo. [source] Solution structure of the bb, domains of human protein disulfide isomeraseFEBS JOURNAL, Issue 5 2009Alexey Y. Denisov Protein disulfide isomerase is the most abundant and best studied of the disulfide isomerases that catalyze disulfide bond formation in the endoplasmic reticulum, yet the specifics of how it binds substrate have been elusive. Protein disulfide isomerase is composed of four thioredoxin-like domains (abb,a,). Cross-linking studies with radiolabeled peptides and unfolded proteins have shown that it binds incompletely folded proteins primarily via its third domain, b,. Here, we determined the solution structure of the second and third domains of human protein disulfide isomerase (b and b,, respectively) by triple-resonance NMR spectroscopy and molecular modeling. NMR titrations identified a large hydrophobic surface within the b, domain that binds unfolded ribonuclease A and the peptides mastoparan and somatostatin. Protein disulfide isomerase-catalyzed refolding of reduced ribonuclease A in vitro was inhibited by these peptides at concentrations equal to their affinity to the bb, fragment. Our findings provide a structural basis for previous kinetic and cross-linking studies which have shown that protein disulfide isomerase exhibits a saturable, substrate-binding site. [source] Peptide-based radiopharmaceuticals: Future tools for diagnostic imaging of cancers and other diseasesMEDICINAL RESEARCH REVIEWS, Issue 3 2004S.M. Okarvi Abstract An Erratum has been published for this article in Medicinal Research Reviews 2004;24:685,686. Small synthetic receptor-binding peptides are the agents of choice for diagnostic imaging and radiotherapy of cancers due to their favorable pharmacokinetics. Molecular modification techniques permit the synthesis of a variety of bioactive peptides with chelating groups, without compromising biological properties. Various techniques have been developed that allow efficient and site-specific labeling of peptides with clinically useful radionuclides such as 99mTc, 123I, 111In, and 18F. Among them, 99mTc is the radionuclide of choice because of its excellent chemical and imaging characteristics. Recently, many 99mTc-labeled peptides have proven to be useful imaging agents. Beside 99mTc-labeled peptides, several peptides radiolabeled with 111In and 123I have been prepared and characterized. In addition, 18F-labeled peptides hold clinical potential due to their ability to quantitatively detect and characterize a variety of human diseases using positron-emission tomography. The availability of this wide range of peptides labeled with different radionuclides offers multiple diagnostic and therapeutic applications. Various receptors are over-expressed in particular tumor types and peptides binding to these receptors can be used to visualize tumor lesions scintigraphically. Thus, radiolabeled peptides have potential use as carriers for the delivery of radionuclides to tumors, infarcts, and infected tissues for diagnostic imaging and radiotherapy. Many radiolabeled peptides are currently under investigation to determine their potential as imaging agents. These peptides are designed mainly for thrombus, tumor, and infection/inflammation imaging. This article presents recent developments in small synthetic peptides for imaging of thrombosis, tumors, and infection/inflammation. © 2004 Wiley Periodicals, Inc. Med Res Rev, 24, No. 3, 357,397, 2004 [source] | ||||||||||