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The aim of this study was to determine whether the severity of contact hypersensitivity reactions (CHSRs) can be observed by noninvasive in vivo optical imaging of matrix metalloproteinase (MMP) activity and whether this is an appropriate tool for monitoring an antiinflammatory effect. Acute and chronic CHSRs were elicited by application of a 1% trinitrochlorobenzene (TNCB) solution for up to five times on the right ear of TNCB-sensitized mice. N-Acetylcysteine (NAC)-treated and sham-treated mice were monitored by measuring ear swelling and optical imaging of MMP activity. In addition, we performed hematoxylin-eosin staining and CD31 immunohistochemistry for histopathologic analysis of the antiinflammatory effects of NAC. The ear thickness and the MMP activity increased in line with the increasing severity of the CHSR. MMP activity was enhanced 2.5- to 2.7-fold during acute CHSR and 3.1- to 4.1-fold during chronic CHSR. NAC suppressed ear swelling and MMP signal intensity in mice with acute and chronic CHSR. During chronic CHSR, the vessel density was significantly reduced in ear sections derived from NAC-treated compared to shamtreated mice. In vivo optical imaging of MMP activity measures acute and chronic CHSR and is useful to monitor antiinflammatory effects [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the impact of different anesthetics on 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) uptake in carcinomas and arthritic ankles. To determine the amount of [18F]FLT uptake in subcutaneous CT26 colon carcinomas or arthritic ankles, spontaneously room air/medical air-breathing mice were anesthetized with isoflurane, a combination of medetomidine/ midazolam, or ketamine/xylazine. Mice were kept conscious or anesthetized during [18]FLT uptake before the 10-minute static positron emission tomographic (PET) investigations. [18F]FLT uptake in CT26 colon carcinomas and arthritic ankles was calculated by drawing regions of interest. We detected a significantly reduced (4.4 ± 0.9 %ID/cm³)[ F]FLT uptake in the carcinomas of ketamine/ xylazine-anesthetized mice compared to the [18F]FLT-uptake in carcinomas of medetomidine/midazolam- (7.0 ± 1.5 %ID/cm³) or isoflurane-anesthetized mice (6.4 ± 1.5 %ID/cm³), whereas no significant differences were observed in arthritic ankles regardless of whether mice were anesthetized or conscious during tracer uptake. The time-activity curves of carcinomas and arthritic ankles yielded diverse [18F]FLT accumulation related to the used anesthetics. [18F]FLT uptake dynamics are different in arthritic ankles and carcinoma, and the magnitude and pharmacokinetics of [18F]FLT uptake are sensitive to anesthetics. Thus, for preclinical in vivo [18F]FLT PET studies in experimental tumor or inflammation models, we recommend the use of isoflurane anesthesia as it yields a stable tracer uptake and is easy to handle. [ABSTRACT FROM AUTHOR]