Purpose: Overexpression of collagen is a hallmark of organ fibrosis. This study describes the pre-clinical evaluation of 4 collagen-targeted PET probes to determine the best candidate for molecular imaging of pulmonary fibrosis. Procedures: The 4 probes are all based on the same peptide sequence, which is known to have good affinity and specificity for collagen. The peptide was conjugated to a cyclic chelator (NODAGA or NOTA) and radiolabeled with Cu-64, Ga-68 or F-18 via complexation of aluminium fluoride. The 4 probes were evaluated in a bleomycin-induced mouse model of pulmonary fibrosis and compared to sham treated animals. In vivo studies include biodistribution, small animal PET-CT imaging, characterization of collagen content and histology. Pharmacokinetics and metabolic stability of the probes were evaluated in healthy rats. Results: CBP7 (Cu-64) and CBP8 (Ga-68) demonstrated fast blood clearance and high stability with respect to metabolism (&gt;85% intact in blood at 2.5 h after injection). They showed 6- to 8-fold greater uptake in the lungs of bleomycin-treated animals compared to controls while the distribution in other organs was similar between bleomycin-treated and control mice at 2.5 h after injection. They both showed renal clearance and low non-target uptake. The two Al18F-labeled probes CBP8 (NODAGA derivative) and CBP9 (NOTA derivative) demonstrated high uptake in lungs of control animals and high non-target uptake in particular in liver and spleen (&gt;13 and &gt;9 %ID/g respectively), suggesting aggregation. Off-target signal in the bone was also evident, especially for CBP8 (&gt;9 %ID/g). This effect was probably due to the partial dissociation of 18F-fluoride from the chelate. Conclusions: We demonstrated that CBP7 and CBP8 are suitable for molecular imaging of pulmonary fibrosis, and represent very promising candidates for bench-to-bedside translation.

Collagen-targeted PET probes for pulmonary fibrosis imaging: Effect of the radioisotope on biodistribution

250th National Meeting (2015)

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