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Title: In vivo hybridization of technetium-99m-labeled peptide nucleic acid (PNA)

Abstract

Hybridization of a radiolabeled single-stranded DNA oligonucleotide with its single-stranded complement in vivo has not yet been convincingly demonstrated. A contributing factor may be unfavorable in vivo properties of the phosphodiester and phosphorothioate DNAs. Peptide nucleic acid (PNA) oligomers have been reported to possess in vivo properties more suitable for radiopharmaceutical applications. We have radiolabeled an amine-derivatized 15-base PNA oligomer with {sup 99m}Tc through a modified MAG{sub 3} chelator. The ability of the PNA to hybridize in vitro with its complement appeared to be unimpaired after conjugation and radiolabeling. Size-exclusion, high-performance liquid chromatography (HPLC) analysis of 37{degree}C serum after 24 hr of incubation showed the radiolabel to be present predominately as labeled PNA with indications of labeled serum proteins and a low molecular weight catabolite. Whole-body clearance in mice was rapid, with 50% of the label eliminated in about 2 hr. After 2.5 hr, the highest uptake (kidneys) was only 1.5% of the injected dose/g; less than 0.07%/g was present in all sampled tissues at 24 hr. To evaluate in vivo hybridization, beads were implanted subcutaneously in both thighs of normal mice. In the left thigh only, the beads were conjugated with complementary single-stranded PNA. At 23 hr following intraperitonealmore » administration of the labeled PNA, the left/right thigh radioactivity ratio was 6:1. Whole-body images at this time showed only bladder, kidneys and the left thigh. Unlike the radiolabeled DNAs investigated in this laboratory, {sup 99m}Tc-PNA displays stability and pharmacokinetic properties suitable for eventual use as radiopharmaceuticals.« less

Authors:
; ;  [1]
  1. Univ. of Massachusetts Medical Center, Worcester, MA (United States); and others
Publication Date:
OSTI Identifier:
560591
Resource Type:
Journal Article
Journal Name:
Journal of Nuclear Medicine
Additional Journal Information:
Journal Volume: 38; Journal Issue: 6; Other Information: PBD: Jun 1997
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; 40 CHEMISTRY; HYBRIDIZATION; IMAGES; IN VIVO; DNA; COMPLEMENT; MICE; PROTEINS; RADIOPHARMACEUTICALS; TECHNETIUM 99; UPTAKE

Citation Formats

Mardirossian, G, Lei, K, and Rusckowski, M. In vivo hybridization of technetium-99m-labeled peptide nucleic acid (PNA). United States: N. p., 1997. Web.
Mardirossian, G, Lei, K, & Rusckowski, M. In vivo hybridization of technetium-99m-labeled peptide nucleic acid (PNA). United States.
Mardirossian, G, Lei, K, and Rusckowski, M. 1997. "In vivo hybridization of technetium-99m-labeled peptide nucleic acid (PNA)". United States.
@article{osti_560591,
title = {In vivo hybridization of technetium-99m-labeled peptide nucleic acid (PNA)},
author = {Mardirossian, G and Lei, K and Rusckowski, M},
abstractNote = {Hybridization of a radiolabeled single-stranded DNA oligonucleotide with its single-stranded complement in vivo has not yet been convincingly demonstrated. A contributing factor may be unfavorable in vivo properties of the phosphodiester and phosphorothioate DNAs. Peptide nucleic acid (PNA) oligomers have been reported to possess in vivo properties more suitable for radiopharmaceutical applications. We have radiolabeled an amine-derivatized 15-base PNA oligomer with {sup 99m}Tc through a modified MAG{sub 3} chelator. The ability of the PNA to hybridize in vitro with its complement appeared to be unimpaired after conjugation and radiolabeling. Size-exclusion, high-performance liquid chromatography (HPLC) analysis of 37{degree}C serum after 24 hr of incubation showed the radiolabel to be present predominately as labeled PNA with indications of labeled serum proteins and a low molecular weight catabolite. Whole-body clearance in mice was rapid, with 50% of the label eliminated in about 2 hr. After 2.5 hr, the highest uptake (kidneys) was only 1.5% of the injected dose/g; less than 0.07%/g was present in all sampled tissues at 24 hr. To evaluate in vivo hybridization, beads were implanted subcutaneously in both thighs of normal mice. In the left thigh only, the beads were conjugated with complementary single-stranded PNA. At 23 hr following intraperitoneal administration of the labeled PNA, the left/right thigh radioactivity ratio was 6:1. Whole-body images at this time showed only bladder, kidneys and the left thigh. Unlike the radiolabeled DNAs investigated in this laboratory, {sup 99m}Tc-PNA displays stability and pharmacokinetic properties suitable for eventual use as radiopharmaceuticals.},
doi = {},
url = {https://www.osti.gov/biblio/560591}, journal = {Journal of Nuclear Medicine},
number = 6,
volume = 38,
place = {United States},
year = {Sun Jun 01 00:00:00 EDT 1997},
month = {Sun Jun 01 00:00:00 EDT 1997}
}