Novel theranostic agent for PET imaging and targeted radiopharmaceutical therapy of tumour-infiltrating immune cells in glioma

Foster, Alexandra; Nigam, Shubhanchi; Tatum, David S.; Raphael, Itay; Xu, Jide; Kumar, Rajeev; Plakseychuk, Elizabeth; Latoche, Joseph D.; Vincze, Sarah; Li, Bo; Giri, Rajan; McCarl, Lauren; Edinger, Robert S.; Ak, Murat; Peddagangireddy, Vishal; Foley, Lesley M.; Hitchens, T. Kevin; Colen, Rivka R.; Pollack, Ian F.; Panigrahy, Ashok; Magda, Darren; Anderson, Carolyn J.; Edwards, Wilson B.; Kohanbash, Gary

doi:10.1016/j.ebiom.2021.103571

Cited by 18 publications

(11 citation statements)

References 59 publications

(76 reference statements)

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“…Further experimental data is certainly required to broaden the application spectrum of this PTA probe. Moreover, the radionuclide theranostic strategy mediated by Lu-177-labeled antibody is also worthy of attention [ 54 , 55 ]. All-in-all, anti-Nectin-4 antibody was shown to be a theranostic carrier, providing an open platform for tumor visualization, screening, and treatment guidance.…”

Section: Disccusionmentioning

confidence: 99%

Nectin-4-targeted immunoSPECT/CT imaging and photothermal therapy of triple-negative breast cancer

et al. 2022

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Background Triple-negative breast cancer (TNBC) is more prone to distant metastasis and visceral recurrence in comparison to other breast cancer subtypes, and is related to dismal prognosis. Nevertheless, TNBC has an undesirable response to targeted therapies. Therefore, to tackle the huge challenges in the diagnosis and treatment of TNBC, Nectin-4 was selected as a theranostic target because it was recently found to be highly expressed in TNBC. We developed anti-Nectin-4 monoclonal antibody (mAbNectin-4)-based theranostic pair, 99mTc-HYNIC-mAbNectin-4 and mAbNectin-4-ICG. 99mTc-HYNIC-mAbNectin-4 was applied to conduct immuno-single photon emission computed tomography (SPECT) for TNBC diagnosis and classification, and mAbNectin-4-ICG to mediate photothermal therapy (PTT) for relieving TNBC tumor growth. Methods Nectin-4 expression levels of breast cancer cells (MDA-MB-468: TNBC cells; and MCF-7, non-TNBC cells) were proved by western blot, flow cytometry, and immunofluorescence imagning. Cell uptake assays, SPECT imaging, and biodistribution were performed to evaluate Nectin-4 targeting of 99mTc-HYNIC-mAbNectin-4. A photothermal agent (PTA) mAbNectin-4-ICG was generated and characterized. In vitro photothermal therapy (PTT) mediated by mAbNectin-4-ICG was conducted under an 808 nm laser. Fluorescence (FL) imaging was performed for mAbNectin-4-ICG mapping in vivo. In vivo PTT treatment effects on TNBC tumors and corresponding systematic toxicity were evaluated. Results Nectin-4 is overexpressed in MDA-MB-468 TNBC cells, which could specifically uptake 99mTc-HYNIC-mAbNectin-4 with high targeting in vitro. The corresponding immunoSPECT imaging demonstrated exceptional performance in TNBC diagnosis and molecular classification. mAbNectin-4-ICG exhibited favourable biocompatibility, photothermal effects, and Nectin-4 targeting. FL imaging mapped biodistribution of mAbNectin-4-ICG with excellent tumor-targeting and retention in vivo. Moreover, mAbNectin-4-ICG-mediated PTT provided advanced TNBC tumor destruction efficiency with low systematic toxicity. Conclusion mAbNectin-4-based radioimmunoimaging provides visualization tools for the stratification and diagnosis for TNBC, and the corresponding mAbNectin-4-mediated PTT shows a powerful anti-tumor effect. Our findings demonstrate that this Nectin-4 targeting strategy offers a simple theranostic platform for TNBC.

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Section: Disccusionmentioning

confidence: 99%

Nectin-4-targeted immunoSPECT/CT imaging and photothermal therapy of triple-negative breast cancer

et al. 2022

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“…To demonstrate the broad applicability of RCA-FRET, we investigated the previously used FRET pair of Tb-Cy5.5 [25][26][27] and the new FRET pair of Eu-ATTO620. Both lanthanide complexes were developed by Lumiphore (see Supporting Figure S1 for chemical structures) [34][35][36] and their NHS-activated complexes were conjugated in house to C6-amino functionalized 5' termini of DNA probes, whereas the dye acceptors (Cy5.5 from GE Healthcare and ATTO620 from ATTO Technology) were directly purchased as 5'-functionalized DNA from Eurogentec. Absorption and emission spectra are shown in Figure 1A.…”

Section: Resultsmentioning

confidence: 99%

Isothermal Rolling Circle Amplification and Lanthanide‐Based FRET for Femtomolar Quantification of MicroRNA

2022

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Quantification of DNA and RNA biomarkers via isothermal amplification technologies can significantly simplify biosensing and clinical diagnostics. However, highly sensitive and washfree assay formats based on time-resolved Förster resonance energy transfer (TR-FRET) have been limited to terbium (Tb) based FRET pairs and their application on specialized clinical instruments. Here, we present the implementation of rolling circle amplification (RCA)-FRET to europium-dye (Eu-ATTO620) FRET pairs and its application on standard benchtop fluorescence plate readers. Eu-ATTO620 RCA-FRET was used to quantify microRNA-21 (miR-21) in a 1 to 100 pM concentration range on a SPARK multimode plate reader system. Detection limits down to 120 � 20 fM (18 � 3 attomol of miR-21) and quantification of endogenous miR-21 from the plasma of ovarian cancer patients using a KRYPTOR clinical plate reader demonstrated the broad applicability and clinical relevance of Eu-dye-based RCA-FRET. The extension to both Eu and Tb based TR-FRET and to standard bioanalytical laboratory instruments has the potential to significantly broaden the application and versatility of RCA-FRET for simple, highly-sensitive, and multiplexed bioanalysis.

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“…More studies with larger cohort and unified standard are necessary to find the best tracer among all the tracers that have already been used in clinical trials for many years. Some newly designed tracers such as 68 Ga-Alb-FAPtp-01 [ 108 ] and 89 Zr/ 177 Lu-labeled Lumi804-aCD11b can be used both in imaging and treatment [ 109 ] . Tracers for glioma imaging are summarized in Table 2 [ 62 – 63 , 65 – 90 , 92 , 94 – 96 , 99 – 106 ] .…”

Section: Discussionmentioning

confidence: 99%

Tracers progress for positron emission tomography imaging of glial-related disease

Jia¹,

Xie²

2022

J Biomed Res

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Glial cells play an essential part in the neuron system. They can not only serve as structural blocks in the human brain but also participate in many biological processes. Extensive studies have shown that astrocytes and microglia play an important role in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, as well as glioma, epilepsy, ischemic stroke, and infections. Positron emission tomography is a functional imaging technique providing molecular-level information before anatomic changes are visible and has been widely used in many above-mentioned diseases. In this review, we focus on the positron emission tomography tracers used in pathologies related to glial cells, such as glioma, Alzheimer's disease, and neuroinflammation.

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Novel theranostic agent for PET imaging and targeted radiopharmaceutical therapy of tumour-infiltrating immune cells in glioma

Cited by 18 publications

References 59 publications

Nectin-4-targeted immunoSPECT/CT imaging and photothermal therapy of triple-negative breast cancer

Nectin-4-targeted immunoSPECT/CT imaging and photothermal therapy of triple-negative breast cancer

Isothermal Rolling Circle Amplification and Lanthanide‐Based FRET for Femtomolar Quantification of MicroRNA

Tracers progress for positron emission tomography imaging of glial-related disease

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