Fluorophor-labeled spermidine derivatives as fluorescent markers in optical tumor imaging

Wolf, Markus; Bauder-Wüst, Ulrike; Pipkorn, Rüdiger; Eskerski, Helmut; Eisenhut, Michael

doi:10.1016/j.bmcl.2006.03.046

Cited by 13 publications

(9 citation statements)

References 16 publications

(24 reference statements)

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“…Therefore, these data provide evidence of the utility of this method to select tumors that might be sensitive to F14512. Fluorophor-labeled polyamine derivatives were already described but were used as probes to study polyamine transport or as markers in optical imaging [36][37][38][39] and not to predict tumor chemosensitivity. We propose to take advantage from this ex vivo method to guide the future clinical selection of patients who might be treated with F14512.…”

Section: Discussionmentioning

confidence: 99%

Preclinical activity of F14512, designed to target tumors expressing an active polyamine transport system

et al. 2009

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We have exploited the polyamine transport system (PTS) to deliver selectively a spermine-drug conjugate, F14512 to cancer cells. This study was aimed to define F14512 anticancer efficacy against tumor models and to investigate whether fluorophor-labeled polyamine probes could be used to identify tumors expressing a highly active PTS and that might be sensitive to F14512 treatments. Eighteen tumor models were used to assess F14512 antitumor activity. Cellular uptake of spermine-based fluorescent probes was measured by flow cytometry in cells sampled from tumor xenografts by needle biopsy. The accumulation of the fluorescent probe within B16 tumors in vivo was assessed using infrared fluorescence imaging. This study has provided evidence of a major antitumor activity for F14512. Significant responses were obtained in 67% of the tumor models evaluated, with a high level of activity recorded in 33% of the responsive models. Complete tumor regressions were observed after i.v., i.p. or oral administrations of F14512 and its antitumor activity was demonstrated over a range of 2-5 dose levels, providing evidence of its good tolerance. The level of cellular fluorescence emitted by the fluorescent probes was higher in cells sampled from tumors sensitive to F14512 treatments than from F14512-refractory tumors. We suggest that these probes could be used to identify tumors expressing a highly active PTS and guide the selection of patients that might be treated with F14512. These results emphasize the preclinical interest of this novel molecule and support its further clinical development.

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Section: Discussionmentioning

confidence: 99%

Preclinical activity of F14512, designed to target tumors expressing an active polyamine transport system

et al. 2009

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“…Wolf et al [15] demonstrated biological characteristic of peptide-acridine conjugates that included acridine yellow G. Cellular toxicity of compounds 24a (aspartate(acridine yellow G)) and 24b (aspartyl(acridine yellow G)spermidine) (Fig. (4)) were tested in tumor cell lines: MH 3924A (rat hepatoma) and B16 (mouse melanoma).…”

Section: -Aminoacridine Yellow G Derivativementioning

confidence: 99%

“…peptide-acridine. New group of fluorescent markers consisted in polyamine (spermidine) transport system in follow to accumulate tumors [15,16].…”

Section: -Aminoacridine Yellow G Derivativementioning

confidence: 99%

“…Carlson et al [19] described the synthesis of peptide-acridine derivatives which started from an appropriate substrate: the receiving acid was used for the preparation of 9-anilinoacridine-4-carboxamide (15) wherein the activated product was attached to the short peptide chain through a linkage to the N-terminus. The needed tripeptide was prepared using standard Fmoc-strategy on Rink amide resin.…”

Section: Solid Phase Synthesismentioning

confidence: 99%

“…Imaging agents can be applied in diagnostic methods to identify infected tissues [15]. Interestingly, bifunctional acridine molecules exhibit unusual chromophoric properties which are associated with participation in selective electron-transfer processes.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Structure-Activity Studies of Peptide-Acridine/Acridone Conjugates

Kukowska-Kaszuba¹,

Dzierzbicka

2007

CMC

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Clickable Polyamine Derivatives as Chemical Probes for the Polyamine Transport System

et al. 2018

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Polyamines are essential for cell growth and differentiation, but their trafficking by the polyamine transport system is not fully understood. Herein, the synthesis of several azido‐derivatized polyamines for easy conjugation by click chemistry is described. Attachment of a 4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene (BODIPY) dye gave fluorescent polyamine probes, which were tested in cell culture. The linear probe series showed superior cellular uptake compared with that of probes in which the dye was attached to a branch on one of the central amines. Interestingly, the linear probes accumulated rapidly in cancer cells (MCF‐7), but not in nontumorigenic cells (MCF‐10A). The fluorescent polyamine probes are therefore applicable to the study of polyamine trafficking, whereas the azido polyamines may be further utilized to transport cargo into cancer cells by exploiting the polyamine transport system.

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Fluorophor-labeled spermidine derivatives as fluorescent markers in optical tumor imaging

Cited by 13 publications

References 16 publications

Preclinical activity of F14512, designed to target tumors expressing an active polyamine transport system

Preclinical activity of F14512, designed to target tumors expressing an active polyamine transport system

Synthesis and Structure-Activity Studies of Peptide-Acridine/Acridone Conjugates

Clickable Polyamine Derivatives as Chemical Probes for the Polyamine Transport System

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