A Conjugate of Pentamethine Cyanine and 18F as a Positron Emission Tomography/Near-Infrared Fluorescence Probe for Multimodality Tumor Imaging

Abstract

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 a 18F-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 with 18F in a quick, one-step reaction, which is important in working with the rapid decay of 18F. 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.

One-Step 18F-Labeling of Estradiol Derivative for PET Imaging of Breast Cancer

“…The good biocompatibility is essential for the application of a PET imaging agent [ 15 ]. Therefore, the cytotoxicity of AmBF 3 -TEG-ES against the human breast cancer cells T47D and MCF-7 was assessed by MTT assay.…”

Recent developments in multimodality fluorescence imaging probes

“…For fluorophores which do not have exchangeable fluoride atoms in their structures, a potential solution for [ 18 F]-labelling is to conjugate a fluorine trapping group to the fluorophore, similar to the appendance of a chelator group to trap radiometal cations. A typical example was seen in recent work by An et al 92 , in which a boronate was used as the F-trapping group and was conjugated to the NIR dye Cy5 by amidation. The boronate was then conveniently converted to arylboron trifluoride in the presence of H[ 18 F] to achieve 18 F-labelling ( Scheme 1 B).…”

“…(A) Synthesis of an 18 F-labelled BODIPY-C 16 /triglyceride 91 . (B) Synthesis of an 18 F-labelled cyanine dye using boronateas as the 18 F-trapping group 92 . …”

Convection Enhanced Delivery for Diffuse Intrinsic Pontine Glioma: Review of a Single Institution Experience

“…Nonetheless, recent developments in synthetic radiochemistry have expanded the library of compounds that can be modified and transformed into theranostics, maintaining the original compound’s bioactivity. For instance, we have experience in generating [ 124 I]- and [ 18 F]-labeled agents [ 74 , 75 , 76 , 77 , 78 , 79 , 80 ]. Of note, the isotope conjugated with the molecule will have great impact on its fate and clinical applicability.…”