Multiple Applications of a Novel Biarsenical Imaging Probe in Fluorescence and PET Imaging of Melanoma

Abstract

A new fluorescent biarsenical peptide labeling probe was synthesized and labeled with the radioactive isotopes 11 C and 18 F. The utility of this probe was demonstrated by installing each of these isotopes into a melanocortin 1 receptor (MC1R) binding peptide, which targets melanoma tumors. Its applicability was further showcased by subsequent in vitro imaging in cells as well as in vivo imaging in melanoma xenograft mice by fluorescence and positron emission tomography.

PET/Fluorescence Imaging: An Overview of the Chemical Strategies to Build Dual Imaging Tools

“…• The dual imaging dye approach: both the fluorophore and the radioisotope are linked together in a unique corestructure before conjugation with the vector • The iterative approach: each "property" is iteratively anchored to build the dual imaging tool • The simultaneous approach: the preparation of the dual imaging tool follows a one-pot process, either by covalent or by noncovalent bonding Whatever the strategy adopted to build the dual imaging tool, coupling and conjugation approaches of the different "properties" will have to meet several requirements: • Achieving the best yields possible when low amounts of radioactive material or expensive biologics are handled • Considering short reaction times when short-lived position emitters are manipulated • Controlling as much as possible the regio-and chemoselectivity of the coupling and conjugation reactions • Preferring mild reaction conditions with sensitive biological vectors • Automating the manufacturing of the dual imaging tools for radioprotection issues Moreover, specificities will be considered and detailed in the next paragraphs for the radiolabeling step depending on the radioisotope used either a radiohalogen ( 18 F or 124 I) or a radiometal ( 68 Ga, 64 Cu, or 89 Zr). The use of 11 C was described in only two examples of dual imaging tools 15,16 and will not be developed here.…”

“…PET imaging has been published, but neither fluorescence imaging nor imaging guided surgery are reported. 16 3.3.1.2. Iterative Approach.…”

“…Moreover, specificities will be considered and detailed in the next paragraphs for the radiolabeling step depending on the radioisotope used either a radiohalogen ( 18 F or 124 I) or a radiometal ( 68 Ga, 64 Cu, or 89 Zr). The use of 11 C was described in only two examples of dual imaging tools , and will not be developed here.…”

“…Only one very recent example approaches this challenge by the preparation of a [ 18 F]­biarsenical fluorescein derivative that is conjugated to a peptide via As–S bond formation. PET imaging has been published, but neither fluorescence imaging nor imaging guided surgery are reported …”

Cyanine-based [18F]F-C-glycosyl dual imaging probe: synthesis, physico-chemical characterization, in vitro binding evaluation and direct [18F]fluorination

“…Some examples of dual PET/FLI imaging probes displaying a [ 18 F]F-C bond were described in the literature with rhodamine, [7][8][9] fluorescein, 10 chalcone, 11 porphyrins, 12 quinoline 13 and cyanine derivatives [14][15][16] as fluorophores, but only two examples of these probes were coupled to a vector. 10,16 From a fluorescence imaging perspective, fluorophores like cyanines, as cyanine 5 derivatives, have appropriate fluorescence excitation/emission properties in the NIR-I optical window in biological tissues (biological window: 650-900 nm). Indeed, scattering, absorption and interference with intrinsic tissue fluorescence can make imaging difficult and limit light penetration.…”