Spray Fluorescent Probes for Fluorescence-Guided Neurosurgery

Kitagawa, Yosuke; Tanaka, Shota; Kuriki, Yugo; Yamamoto, K.; Ogasawara, Akira; Nejo, Takahide; Matsuura, Reiko; Koike, Tsukasa; Hana, Taijun; Takahashi, Satoshi; Nomura, Masashi; Takayanagi, Shunsaku; Mukasa, Akitake; Kamiya, Mako; Urano, Yasuteru; Saito, Nobuhito

doi:10.3389/fonc.2019.00727

Cited by 10 publications

(10 citation statements)

References 19 publications

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“…In the removal of solid tumors and the preservation of healthy tissues during surgery, the application of fluorescent dyes such as Indocyanine Green (ICG) and the protoporphyrin IX precursor 5-aminolevulinic acid (5-ALA) has notable clinical utility. However, the feasibility of applying always-on fluorescent probes in the fluorescence-guided surgery context, especially in the form of topical sprays can be impaired by low target specificity and high background fluorescence . Activatable fluorescent probes such as enzyme-cleavable probes or pH-activable probes showed promising results in the accurate determination of tumor margins in situ . , Moreover, recent developments of multivariate AND-gate optical contrast agents, which produce a signal upon least at two proteolytic processes may further enhance the contrast between the tumor boundaries and surrounding healthy tissues …”

Section: Discussionmentioning

confidence: 99%

Silicon-Rhodamine Functionalized Evocalcet Probes Potently and Selectively Label Calcium Sensing Receptors In Vitro, In Vivo, and Ex Vivo

Bátora,

Fischer,

Kaderli

et al. 2024

ACS Pharmacol. Transl. Sci.

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The calcium sensing receptor (CaSR) is a ubiquitously expressed G-protein coupled receptor (GPCR) that regulates extracellular calcium signals via the parathyroid glands. CaSR has recently also been implicated in noncalcitropic pathophysiologies like asthma, gut inflammation, and cancer. To date, molecular tools that enable the bioimaging of CaSR in tissues are lacking. Based on in silico analyses of available structure− activity relationship data on CaSR ligands, we designed and prepared silicon-rhodamine (SiR) conjugates of the clinically approved drug evocalcet. The new probes EvoSiR4 and EvoSiR6, with differing linker lengths at the evocalcet carboxyl end, both showed a 6-fold and 3-fold increase in potency toward CaSR (EC 50 < 45 nM) compared to evocalcet and the evocalcet-linker conjugate, respectively, in an FLIPR-based cellular functional assay. The specificity of the EvoSiR probes toward CaSR binding and the impact of albumin was evaluated in live cell experiments. Both probes showed strong albumin binding, which facilitated the clearance of nonspecific binding interactions. Accordingly, in zebrafish embryos, EvoSiR4 specifically labeled the high CaSR expressing neuromasts of the lateral line in vivo. EvoSiR4 was also assessed in human parathyroid tissues ex vivo, showing a specific absolute CaSR-associated fluorescence compared to that of parathyroid autofluorescence. In summary, functionalization of evocalcet by SiR led to the preparation of potent and specific fluorescent CaSR probes. EvoSiR4 is a versatile small-molecular probe that can be employed in CaSR-related biomedical analyses where antibodies are not applicable.

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Section: Discussionmentioning

confidence: 99%

Silicon-Rhodamine Functionalized Evocalcet Probes Potently and Selectively Label Calcium Sensing Receptors In Vitro, In Vivo, and Ex Vivo

Bátora,

Fischer,

Kaderli

et al. 2024

ACS Pharmacol. Transl. Sci.

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“…Additionally, the proposed administration route for PH08 is to topically spray onto tissue surfaces that are suspected to harbor tumors; requiring about a tenfold lower dose than systemic administration. [ 62 , 63 , 64 ] In addition, since PH08 shows durable retention in organelles, its fluorescence signal is stable for at least 4 h after application. With this feature, it can also be used for laparoscopic or open surgery of peritoneal dissemination of ovarian and gastrointestinal cancer.…”

Section: Discussionmentioning

confidence: 99%

Topical pH Sensing NIR Fluorophores for Intraoperative Imaging and Surgery of Disseminated Ovarian Cancer

et al. 2022

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Fluorescence‐guided surgery (FGS) aids surgeons with real‐time visualization of small cancer foci and borders, which improves surgical and prognostic efficacy of cancer. Despite the steady advances in imaging devices, there is a scarcity of fluorophores available to achieve optimal FGS. Here, 1) a pH‐sensitive near‐infrared fluorophore that exhibits rapid signal changes in acidic tumor microenvironments (TME) caused by the attenuation of intramolecular quenching, 2) the inherent targeting for cancer based on chemical structure (structure inherent targeting, SIT), and 3) mitochondrial and lysosomal retention are reported. After topical application of PH08 on peritoneal tumor regions in ovarian cancer‐bearing mice, a rapid fluorescence increase (< 10 min), and extended preservation of signals (> 4 h post‐topical application) are observed, which together allow for the visualization of submillimeter tumors with a high tumor‐to‐background ratio (TBR > 5.0). In addition, PH08 is preferentially transported to cancer cells via organic anion transporter peptides (OATPs) and colocalizes in the mitochondria and lysosomes due to the positive charges, enabling a long retention time during FGS. PH08 not only has a significant impact on surgical and diagnostic applications but also provides an effective and scalable strategy to design therapeutic agents for a wide array of cancers.

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“…[21,27,39] Compared with intravenous injection, topical administration allows for rapid identification of neoplastic lesions at a very low dose, reducing systemic exposure and potential toxicity. [132] However, due to the limited penetration depth, topically administered probes can only highlight the structures at the surface where they are applied, and tumor detection might be detrimentally affected by mucus consistency and bowel cleanliness. [126] Since activatable fluorescent probes are nonfluorescent without enzymatic cleavage, there is no need to wash out the unreacted agents.…”

Section: Route Of Administrationmentioning

confidence: 99%

Current trends and key considerations in the clinical translation of targeted fluorescent probes for intraoperative navigation

Liu

et al. 2021

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The rapid development of fluorescence imaging for intraoperative navigation has spurred further development of targeted fluorescent probes in the past decade. Only a few nontargeted dyes, including indocyanine green and methylene blue, are currently applied for fluorescence guided surgery in the clinic. While no targeted fluorescent probes have been approved for the clinic, a number of them have entered clinical trials. These probes have emission wavelengths in the visible and near infrared (NIR)‐I (700‐900 nm) range. Among them, activatable probes and nanoprobes have generated special interest. Compared with NIR‐I fluorescent probes, NIR‐II (1000‐1700 nm) fluorescent probes exhibit better intravital performance in terms of increased penetration depths, reduced tissue autofluorescence, and higher signal‐to‐background ratios. However, more challenges are expected before the successful translation of NIR‐II probes from bench to bedside. This review provides a brief overview of targeted fluorescent probes under clinical evaluation and recent achievements in the field of NIR‐II fluorescence imaging. In addition, we outline key considerations concerning the design of fluorescent probes for clinical translation.

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Spray Fluorescent Probes for Fluorescence-Guided Neurosurgery

Cited by 10 publications

References 19 publications

Silicon-Rhodamine Functionalized Evocalcet Probes Potently and Selectively Label Calcium Sensing Receptors In Vitro, In Vivo, and Ex Vivo

Silicon-Rhodamine Functionalized Evocalcet Probes Potently and Selectively Label Calcium Sensing Receptors In Vitro, In Vivo, and Ex Vivo

Topical pH Sensing NIR Fluorophores for Intraoperative Imaging and Surgery of Disseminated Ovarian Cancer

Current trends and key considerations in the clinical translation of targeted fluorescent probes for intraoperative navigation

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