espiratory syncytial virus (RSV) is the most frequent R cause of lower respiratory tract illness in infants and young children. Early studies in adults indicated that RSV infection was associated with a mild illness resembling the common cold.' Later studies, however, demonstrated that infection could be associated with significant morbidity, absenteeism, and prolonged alterations in airway resistance.' It has also been reported that RSV infection may cause severe or fatal pneumonia in adults immunocompromised as the result of organ transplantation, hematologic malignancy, or HIV infe~tion.~-~ In the last 15 years, a number of studies have also demonstrated that RSV infection may be associated with a clinically significant, influenza-like illness in residents of longterm care Early reports described several outbreaks of RSV infection that were investigated retrospectively after the onset of respiratory illness in a large number of resident~.'~~*''-'~ In general, the diagnosis of RSV was established serologically, and evidence of other respiratory viruses was not detected. Attack rates were high (19 to 43%), and the illnesses were of variable severity. In the most severe outbreak, 40 of 101 residents in a nursing home developed respiratory illness; among those who became ill, 55% developed radiographically proven pneumonia, and 20% died.13 Prospective studies of respiratory illnesses in nursing homes have also detected the presence of RSV infection. In most of these studies, RSV was implicated in a minority of i l l n e s~e s .~~'~~'~ However, one recent study found RSV to be the predominant respiratory virus identified during an influenza season.'' In that study, 149 illnesses were studied in a 591-bed nursing home. Sixty-two illnesses were determined to be of viral etiology, and of these, 40 were attributed to RSV and only two to influenza. The same investigators evaluated acute and convalescent serum obtained from ill residents in two nursing homes." The proportion of ill residents with serologic evidence of RSV infection varied widely, from 3% in one nursing home to 20% in the second facility. Supported by NIH grants AGO9632 (SG), AGO0548 (SG), and SAG00213 (TW)This is GRECC publication number 9406.

Background: Myocardial infarction (MI) evokes an organized remodeling process characterized by the activation and transdifferentiation of quiescent cardiac fibroblasts to generate a stable collagen rich scar. Early fibroblast activation may be amenable to targeted therapy, but is challenging to identify in vivo. We aimed to non-invasively image active fibrosis by targeting the fibroblast activation protein (FAP) expressed by activated (myo)fibroblasts, using a novel positron emission tomography (PET) radioligand [ 68 Ga]MHLL1 after acute MI. Methods: One-step chemical synthesis and manual as well as module-based radiolabeling yielded [ 68 Ga]MHLL1. Binding characteristics were evaluated in murine and human FAP-transfected cells, and stability tested in human serum. Biodistribution in healthy animals was interrogated by dynamic PET imaging, and metabolites were measured in blood and urine. The temporal pattern of FAP expression was determined by serial PET imaging at 7 d and 21 d after coronary artery ligation in mice as percent injected dose per gram (%ID/g). PET measurements were validated by ex vivo autoradiography and immunostaining for FAP and inflammatory macrophages. Results: [ 68 Ga]MHLL1 displayed specific uptake in murine and human FAP-positive cells (p = 0.0208). In healthy mice the tracer exhibited favorable imaging characteristics, with low blood pool retention and dominantly renal clearance. At 7 d after coronary artery ligation, [ 68 Ga]MHLL1 uptake was elevated in the infarct relative to the non-infarcted remote myocardium (1.3 ± 0.3 vs. 1.0 ± 0.2 %ID/g, p < 0.001) which persisted to 21 d after MI (1.3 ± 0.4 vs. 1.1 ± 0.4 %ID/g, p = 0.013). Excess unlabeled compound blocked tracer accumulation in both infarct and non-infarct remote myocardium regions (p < 0.001). Autoradiography and histology confirmed the regional uptake of [ 68 Ga]MHLL1 in the infarct and especially border zone regions, as identified by Masson trichrome collagen staining. Immunostaining further delineated persistent FAP expression at 7 d and 21 d post-MI in the border zone, consistent with tracer distribution in vivo. Conclusion:The simplified synthesis of [ 68 Ga]MHLL1 bears promise for non-invasive characterization of fibroblast activation protein early in remodeling after MI.

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