Pulmonary fibrosis is a scarring of the lungs that can arise from radiation injury, drug toxicity, environmental or genetic causes, and for unknown reasons [idiopathic pulmonary fibrosis (IPF)]. Overexpression of collagen is a hallmark of organ fibrosis. Here, we describe a peptide-based PET probe (68Ga-CBP8) that targets collagen type I. We evaluated 68Ga-CBP8 in vivo in the bleomycin-induced mouse model of pulmonary fibrosis. 68Ga-CBP8 showed high specificity for pulmonary fibrosis and high target:background ratios in diseased animals. The lung PET signal and lung 68Ga-CBP8 uptake (quantified ex vivo) correlated linearly (r2=0.80) with the amount of lung collagen in mice with fibrosis. We further demonstrated that the 68Ga-CBP8 probe could be used to monitor response to treatment in a second mouse model of pulmonary fibrosis associated with vascular leak. Ex vivo analysis of lung tissue from patients with IPF supported the animal findings. These studies indicate that 68Ga-CBP8 is a promising candidate for non-invasive imaging of human pulmonary fibrosis.

Objective We examined whether severity scores (1SD vs. 2SDs) of a unique profile of the Child Behavior Checklist (CBCL) consisting of the Anxiety/Depression, Aggression, and Attention (A-A-A) scales would help differentiate levels of deficits in children with ADHD. Study Design Subjects were 197 children with and 224 without ADHD. We defined deficient emotional selfregulation (DESR) as an aggregate cut-off score of >180 but <210 (1SD) on the A-A-A scales of the CBCL (CBCL-DESR) and Severe Dysregulation as an aggregate cut-off score of ≥210 on the same scales (CBCL-Severe Dysregulation). All subjects were assessed with structured diagnostic interviews and a range of functional measures. Results 36% of children with ADHD had a positive CBCL-DESR profile vs. 2% of controls (p<0.001) and 19% had a positive CBCL-Severe Dysregulation profile vs. 0% of controls (p<0.001). The subjects positive for the CBCL-Severe Dysregulation profile differed selectively from those with the CBCL-DESR profile in having higher rates of unipolar and bipolar mood disorders, oppositional defiant and conduct disorders, psychiatric hospitalization at both baseline and follow up assessments, and a higher rate of the CBCL-Severe Dysregulation in siblings. In contrast, the CBCL-DESR was associated with higher rates of comorbid disruptive behavior, anxiety disorders, and impaired interpersonal functioning compared to other ADHD children. Conclusion Severity scores of the A-A-A CBCL profiles can help distinguish two groups of emotional regulation problems in children with ADHD.

Participants with ADHD were significantly more likely to repeat a grade, adjusting for all other variables indicating the critical importance of early identification of ADHD to help mitigate adverse educational outcomes.