A new optical imaging probe targeting αVβ3 integrin in glioblastoma xenografts

Lanzardo, Stefania; Conti, Laura; Brioschi, Chiara; Bartolomeo, Maria Paola; Belvisi, Laura; Manzoni, Leonardo; Maiocchi, Alessandro; Maisano, Federico; Forni, Guido

doi:10.1002/cmmi.444

Cited by 45 publications

(43 citation statements)

References 36 publications

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“…Thirty studies described the results of fluorescent agents in a pre-clinical phase (Table 2) [2, 4, 7, 8, 10, 18–21, 32, 43, 45–48, 51, 55, 61, 68, 73, 77, 83, 90, 91, 104, 108, 111, 112, 116, 121]. Within this group of fluorescent agents, a broad distinction could be made between molecular fluorophores and nanoparticles.…”

Section: Resultsmentioning

confidence: 99%

Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

et al. 2016

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BackgroundFluorescence-guided surgery (FGS) is a technique used to enhance visualization of tumor margins in order to increase the extent of tumor resection in glioma surgery. In this paper, we systematically review all clinically tested fluorescent agents for application in FGS for glioma and all preclinically tested agents with the potential for FGS for glioma.MethodsWe searched the PubMed and Embase databases for all potentially relevant studies through March 2016. We assessed fluorescent agents by the following outcomes: rate of gross total resection (GTR), overall and progression-free survival, sensitivity and specificity in discriminating tumor and healthy brain tissue, tumor-to-normal ratio of fluorescent signal, and incidence of adverse events.ResultsThe search strategy resulted in 2155 articles that were screened by titles and abstracts. After full-text screening, 105 articles fulfilled the inclusion criteria evaluating the following fluorescent agents: 5-aminolevulinic acid (5-ALA) (44 studies, including three randomized control trials), fluorescein (11), indocyanine green (five), hypericin (two), 5-aminofluorescein-human serum albumin (one), endogenous fluorophores (nine) and fluorescent agents in a pre-clinical testing phase (30). Three meta-analyses were also identified.Conclusions5-ALA is the only fluorescent agent that has been tested in a randomized controlled trial and results in an improvement of GTR and progression-free survival in high-grade gliomas. Observational cohort studies and case series suggest similar outcomes for FGS using fluorescein. Molecular targeting agents (e.g., fluorophore/nanoparticle labeled with anti-EGFR antibodies) are still in the pre-clinical phase, but offer promising results and may be valuable future alternatives.

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Section: Resultsmentioning

confidence: 99%

Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

et al. 2016

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“…In a subcutaneous U-87 MG xenograft model, RGD peptides conjugated to Cy5.5 label glioma cells with a high TNR after 4 hours. 92, 93 A Cy5.5 conjugated non-peptide RGD mimetic is similarly effective at labeling U-87 MG xenografts. 94 In an orthotopic glioma model, RGD-Cy5.5 labeled tumor cells with a TNR of 2.64 +/− 0.20 two hours after injection.…”

Section: Targeted Fluorescent Molecular Imaging Agentsmentioning

confidence: 97%

Fluorescent-Guided Surgical Resection of Glioma with Targeted Molecular Imaging Agents: A Literature Review

et al. 2016

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The median life expectancy following a diagnosis of glioblastoma (GBM) is 15 months. While chemotherapeutics may someday cure GBM by killing the highly dispersive malignant cells, the most important contribution that clinicians can currently offer to improve survival is by maximizing the extent of resection and providing concurrent chemo-radiation, which has become standard. Strides have been made in this area with the advent and implementation of methods of improved intraoperative tumor visualization. One of these techniques, optical fluorescent imaging with targeted molecular imaging agents, allows the surgeon to view fluorescently labeled tumor tissue during surgery with the use of special microscopy – thereby highlighting where to resect, and indicating when tumor-free margins have been obtained. This advantage is especially important at the difficult to observe margins where tumor cells infiltrate normal tissue. Targeted fluorescent agents also may be valuable for identifying tumor versus non-tumor tissue. In this review, we briefly summarize non-targeted fluorescent tumor imaging agents before discussing several novel targeted fluorescent agents being developed for glioma imaging in the context of fluorescent guided surgery or live molecular navigation. Many of these agents are currently undergoing preclinical testing. As the agents become available, however, it is necessary to understand the strengths and weaknesses of each.

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“…Forni et al reported a NIR fluorescence RGD cyclic probe 39 for noninvasive detection of a v b 3 integrin-overexpressing tumors. 141 The targeting moiety was a functionalized cRGD peptide that preferentially bound the Mn-activated form of integrin, mediating rapid and extensive cell adhesion. The conjugate displayed a high binding affinity for a v b 3 integrin on human U-87 MG glioblastoma cells and their xenografts in nude mice.…”

mentioning

confidence: 99%

Fluorescent chemical probes for accurate tumor diagnosis and targeting therapy

et al. 2017

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Surgical resection of solid tumors is currently the gold standard and preferred therapeutic strategy for cancer. Chemotherapy drugs also make a significant contribution by inhibiting the rapid growth of tumor cells and these two approaches are often combined to enhance treatment efficacy. However, surgery and chemotherapy inevitably lead to severe side effects and high systemic toxicity, which in turn results in poor prognosis. Precision medicine has promoted the development of treatment modalities that are developed to specifically target and kill tumor cells. Advances in in vivo medical imaging for visualizing tumor lesions can aid diagnosis, facilitate surgical resection, investigate therapeutic efficacy, and improve prognosis. In particular, the modality of fluorescence imaging has high specificity and sensitivity and has been utilized for medical imaging. Therefore, there are great opportunities for chemists and physicians to conceive, synthesize, and exploit new chemical probes that can image tumors and release chemotherapy drugs in vivo. This review focuses on small molecular ligand-targeted fluorescent imaging probes and fluorescent theranostics, including their design strategies and applications in clinical tumor treatment. The progress in chemical probes described here suggests that fluorescence imaging is a vital and rapidly developing field for interventional surgical imaging, as well as tumor diagnosis and therapy.

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A new optical imaging probe targeting α_Vβ₃ integrin in glioblastoma xenografts

Cited by 45 publications

References 36 publications

Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

Fluorescent-Guided Surgical Resection of Glioma with Targeted Molecular Imaging Agents: A Literature Review

Fluorescent chemical probes for accurate tumor diagnosis and targeting therapy

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