A conjugate of pentamethine cyanine and¹⁸F as a positron emission tomography/near-infrared fluorescence probe for multimodality tumor imaging

The novel synthesis of a dual-modality, pentamethine cyanine (Cy5) fluorescent,¹⁸F positron emission tomography (PET) imaging probe is reported. The probe shows a large extinction coefficient and large quantum yield in the biologically transparent, near-infrared window (650-900 nm) for in vivo fluorescent imaging. This fluorophore bears the isotope,¹⁸F, giving a¹⁸F-PET/near-infrared fluorescent (NIRF), bi-modal imaging probe, that combines the long-term stability of NIRF and the unlimited penetration depth of PET imaging. The bi-modal probe is labeled with¹⁸F in a quick, one-step reaction, which is important in working with the rapid decay of¹⁸F. The bi-modal probe bears a free carboxyl group, highlighting a PET/NIRF synthon that can be conjugated onto many advanced biomolecules for biomarker-specific in vivo dual-modal PET/NIR tumor imaging, confocal histology, and utility in multi-fluorophore, fluorescence-guided surgery. Its potential in vivo biocompatibility is explored in a quick proof-of-principal in vivo study. The dye is delivered to A549 xenograft flank-tumors to generate PET and NIRF signals at the tumor site. The tumor distribution is confirmed in ex vivo gamma counting and imaging. Pentamethine cyanine (Cy5) has the ability to preferentially accumulate in tumor xenografts. We substitute the PET/NIRF probe for Cy5, and explore this phenomenon.