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99mTc-technetium labeling of antiarthritic peptides to evaluate homing and biodistribution at inflamed joints.

Abstract：

PURPOSE:The aim of this study was to investigate the biodistribution and localization of an anti-inflammatory nonapeptide coupled to synovial targeting peptide (HAP-1) in rat adjuvant-induced arthritis. PROCEDURE:N(ε)-functionalized histidine derivative was coupled to the N-terminus of core peptide (CP) and HAP-1 to allow coupling of (99m)Tc-tricarbonyl linker (Isolink). Synovial homing peptide HAP-1 was linked to CP through a peptide bond prior to labeling with (99m)Tc. Peptides were purified by high-performance liquid chromatography, characterized by mass spectrometry, radiolabeled and injected into normal and arthritic rats to determine biodistribution and localization. RESULTS:Gamma scintigraphy imaging showed that the biodistribution of all (99m)Tc-labeled peptides were higher in the arthritic joints compared with the normal nonarthritic joints, at all three time points (10 min, 1 h, 3 h postinjection) and attributed to increased blood flow to inflammatory sites. HAP-1 and CP-HAP-1 showed a greater uptake and localization to arthritic joints compared with controls. There was no difference in the physiological biodistribution of these agents in the heart, kidneys and the bladder. CONCLUSIONS:This study highlights the versatility of using the His derivative linker for (99m)Tc tagging of a variety of peptides. It also demonstrates greater peptide localization and thereby bioavailability of therapeutic peptides to inflamed joints following specific conjugation to homing peptides. The ability to localize peptide/drugs to inflamed synovium has important therapeutic implications.

journal_name

Nucl Med Biol

journal_title

Nuclear medicine and biology

authors

Ali M,Vanniasinghe A,Kumar V,Barnett R,Alberto R,Manolios N

doi

10.1016/j.nucmedbio.2011.01.007

subject

Has Abstract

pub_date

2011-07-01 00:00:00

pages

751-6

issue

5

eissn

0969-8051

issn

1872-9614

pii

S0969-8051(11)00032-1

journal_volume

38

pub_type

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