Abstract
297
Introduction: Excessive collagen deposition is the hallmark of fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). Current radiologic methods detect established scar (fibrosis) but are unable to distinguish between new versus old scar with any single measure. We developed a positron emission technology (PET) tracer, termed 68Ga-CBP8, that binds type I collagen with high affinity and specificity.1 68Ga-CBP8, can detect and stage pulmonary fibrosis in a mouse model and measure treatment response. Our data suggest that this probe recognizes freshly synthesized as opposed to mature, established collagen. Here we performed first in human studies of 68Ga-CBP8 to assess safety and tracer distribution in healthy volunteers and ability to detect increased collagen deposition in subjects with IPF, the most common form of pulmonary fibrosis.
Methods: 68Ga-CBP8 PET and simultaneous magnetic resonance imaging (MRI) was performed in 5 healthy volunteers and 8 subjects with IPF using the Biograph mMR scanner (Siemens Healthineers, Erlangen, Germany). ~250 MBq (range 156-433 MBq) of 68Ga-CBP8 was administered and emission data were acquired for up to 2 hours in listmode format. The images corresponding to 35 dynamic frames (6×10, 4×30, 5×60, 6×120 and 14×300 seconds) were reconstructed using the standard reconstruction algorithm (OSEM, 21 subsets, 3 iterations, 256×256 matrix size, 127 slices) and smoothed with a 4 mm FHWM Gaussian filter. Attenuation correction was performed using the MR-based method provided by the manufacturer. Test re-test was performed in 3 IPF subjects up to a two-week time interval.
Results: Our initial experience is that 68Ga-CBP8 is well-tolerated and safe. The tracer is rapidly renally cleared with low background uptake in lungs of healthy volunteers. No unexpected off target tracer uptake was detected. Preliminary analyses demonstrate that whole lung standardized uptake values (SUVs) are increased in IPF subjects compared to healthy volunteers when measured 1-hour post injection (SUV 0.71 +/- 0.06 vs 0.42 +/- 0.15, p = 0.002). In contrast to healthy volunteers where lung PET signal was low and uniform, in IPF subjects the PET signal was higher and heterogenous (Figure - left panel). Test to test reproducibility was excellent with less than 5% average variation between tests (Figure - right panel).
Conclusions: We have developed the ability to perform collagen-targeted PET imaging in humans to detect collagen deposition in pulmonary fibrosis. 68Ga-CBP8 is safe and displays excellent tracer characteristics. Further work is needed to assess for associations between degree of tracer uptake and clinical outcomes and to determine if 68Ga-CBP8 can detect early response to fibrotic-targeted therapies.