11C-Para-aminobenzoic acid PET imaging of S. aureus and MRSA infection in preclinical models and humans

被引:25
作者
Ordonez, Alvaro A. [1 ,2 ]
Parker, Matthew F. L. [3 ]
Miller, Robert J. [4 ]
Plyku, Donika [5 ]
Ruiz-Bedoya, Camilo A. [1 ,2 ]
Tucker, Elizabeth W. [1 ,6 ]
Luu, Justin M. [3 ]
Dikeman, Dustin A. [4 ]
Lesniak, Wojciech G. [5 ]
Holt, Daniel P. [5 ]
Dannals, Robert F. [5 ]
Miller, Lloyd S. [4 ]
Rowe, Steven P. [5 ]
Wilson, David M. [3 ]
Jain, Sanjay K. [1 ,2 ,5 ]
机构
[1] Johns Hopkins Univ, Ctr Infect & Inflammat Imaging Res, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Dept Pediat, Sch Med, Baltimore, MD 21205 USA
[3] UCSF, Dept Radiol & Biomed Imaging, San Francisco, CA USA
[4] Johns Hopkins Univ, Dept Dermatol, Baltimore, MD USA
[5] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA
[6] Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Sch Med, Baltimore, MD USA
关键词
PARA-AMINOBENZOIC ACID; RADIOTRACER; MARKER;
D O I
10.1172/jci.insight.154117
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Tools for noninvasive detection of bacterial pathogens are needed but are not currently available for clinical use. We have previously shown thatpara-aminobenzoic acid (PABA) rapidly accumulates in a wide range of pathogenic bacteria, motivating the development of related PET radiotracers. In this study, C-11-PABA PET imaging was used to accurately detect and monitor infections due to pyogenic bacteria in multiple clinically relevant animal models. C-11-PABA PET imaging selectively detected infections in muscle, intervertebral discs, and methicillin-resistant Staphylococcus aureus-infected orthopedic implants. In what we believe to be first-in-human studies in healthy participants, C-11-PABA was safe, well-tolerated, and had a favorable biodistribution, with low background activity in the lungs, muscles, and brain. C-11-PABA has the potential for clinical translation to detect and localize a broad range of bacteria.
引用
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页数:12
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共 38 条
[1]  
BENNER EJ, 1968, LANCET, V2, P741
[2]   MIRD Pamphlet No. 21: A Generalized Schema for Radiopharmaceutical Dosimetry-Standardization of Nomenclature [J].
Bolch, Wesley E. ;
Eckerman, Keith F. ;
Sgouros, George ;
Thomas, Stephen R. .
JOURNAL OF NUCLEAR MEDICINE, 2009, 50 (03) :477-484
[3]   STUDIES IN PARA-AMINOHIPPURIC ACID SYNTHESIS IN THE HUMAN - ITS APPLICATION AS A LIVER FUNCTION TEST [J].
DEISS, WP ;
COHEN, PP .
JOURNAL OF CLINICAL INVESTIGATION, 1950, 29 (08) :1014-1020
[4]   GLYCINE CONJUGATION OF PARA-AMINOBENZOIC ACID (PABA) - A QUANTITATIVE TEST OF LIVER-FUNCTION [J].
FURUYA, KN ;
DURIE, PR ;
ROBERTS, EA ;
SOLDIN, SJ ;
VERJEE, Z ;
YUNGJATO, L ;
GIESBRECHT, E ;
ELLIS, L .
CLINICAL BIOCHEMISTRY, 1995, 28 (05) :531-540
[5]   Rabbit model of Staphylococcus aureus implant-associated spinal infection [J].
Gordon, Oren ;
Miller, Robert J. ;
Thompson, John M. ;
Ordonez, Alvaro A. ;
Klunk, Mariah H. ;
Dikeman, Dustin A. ;
Joyce, Daniel P. ;
Ruiz-Bedoya, Camilo A. ;
Miller, Lloyd S. ;
Jain, Sanjay K. .
DISEASE MODELS & MECHANISMS, 2020, 13 (07)
[6]   Molecular Imaging: a Novel Tool To Visualize Pathogenesis of Infections In Situ [J].
Gordon, Oren ;
Ruiz-Bedoya, Camilo A. ;
Ordonez, Alvaro A. ;
Tucker, Elizabeth W. ;
Jain, Sanjay K. .
MBIO, 2019, 10 (05)
[7]   Radiosynthesis and validation of [Carboxy-11C]4-Aminobenzoic acid ([11C]PABA), a PET radiotracer for imaging bacterial infections [J].
Holt, Daniel P. ;
Kalinda, Alvin S. ;
Bambarger, Lauren E. ;
Jain, Sanjay K. ;
Dannals, Robert F. .
JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 2019, 62 (01) :28-33
[8]   Elucidation of the Intestinal Absorption of para-Aminobenzoic Acid, a Marker for Dietary Intake [J].
Imai, Teruko ;
Tanaka, Keiichiro ;
Yonemitsu, Takahiro ;
Yakushiji, Yuta ;
Ohura, Kayoko .
JOURNAL OF PHARMACEUTICAL SCIENCES, 2017, 106 (09) :2881-2888
[9]   para-aminobenzoic acid used as a marker for completeness of 24 hour urine: Assessment of control limits for a specific HPLC method [J].
Jakobsen, J ;
Ovesen, L ;
Fagt, S ;
Pedersen, AN .
EUROPEAN JOURNAL OF CLINICAL NUTRITION, 1997, 51 (08) :514-519
[10]   A Modified Chronic Infection Model for Testing Treatment of Staphylococcus aureus Biofilms on Implants [J].
Jorgensen, Nis Pedersen ;
Meyer, Rikke ;
Dagnaes-Hansen, Frederik ;
Fuursted, Kurt ;
Petersen, Eskild .
PLOS ONE, 2014, 9 (10)