Evaluation of Ac-Lys0(IRDye800CW)Tyr3-octreotate as a novel tracer for SSTR2-targeted molecular fluorescence guided surgery in meningioma

Dijkstra, Bianca M.; Jong, Marion de; Stroet, Marcus C. M.; Andreae, Fritz; Dulfer, Sebastiaan E.; Everts, Maaike; Kruijff, Schelto; Nonnekens, Julie; Dunnen, Wilfred F. A. den; Kruyt, Frank A.E.; Groen, Rob J. M.

doi:10.1007/s11060-021-03739-1

Cited by 7 publications

(12 citation statements)

References 37 publications

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“…In our previous publication, we determined that the IC 50 values for SSTR 2 were 72 nM for 800CW-TATE and 2.5 nM for DOTA-TATE [ 13 ]. In vitro binding of 800CW-TATE on plated cells was demonstrated (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…It was observed that the fluorescent signal was highest in the disrupted regions of the tissue sections. NCI-H69 tumors have a well-established expression of SSTR 2 whereas CH-157MN are SSTR 2 -negative [ 13 ]. However, co-incubation with DOTA-TATE did not block the fluorescence signal from 800CW-TATE in the NCI-H69 sections.…”

Section: Resultsmentioning

confidence: 99%

“…800CW-TATE was studied as a novel contrast agent for molecular, fluorescence-guided, surgery (MFGS) on NCI-H69 tumor xenograft-bearing mice. In this model, the tracer was able to detect tumor tissue for MFGS [ 13 ]. To verify SSTR 2 specific binding to the tumor, a blocking experiment was performed by pre-administration of DOTA-TATE, thereby outcompeting 800CW-TATE for binding to SSTR 2 .…”

Section: Resultsmentioning

confidence: 99%

“…Tumor tissue from mice described in another publication was used [ 13 ]. Briefly, BALB/c-nu mice were inoculated with 5 * 10 6 human small cell lung cancer cells (NCI-H69) in 1:1 medium: matrigel [ 13 , 14 , 21 ]. When the tumors reached a size of 400 mm 3 , 800CW-TATE (3 µg, 1.36 nmol, 50 µL saline) was injected retro-orbitally.…”

Section: Methodsmentioning

confidence: 99%

“…Here, we describe dead cell-binding of Ac-Lys 0 (IRDye800CW)-Tyr 3 -octreotate (800CW-TATE, Fig. 1 ), a contrast agent for molecular fluorescence-guided surgery of meningiomas [ 13 ]. IRDye800CW is a widely applied fluorescent cyanine dye, which has fluorescent properties in the near-infrared region (NIR, absorption: 774 nm, emission: 789 nm).…”

Section: Introductionmentioning

confidence: 99%

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Necrosis binding of Ac-Lys0(IRDye800CW)-Tyr3-octreotate: a consequence from cyanine-labeling of small molecules

et al. 2021

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Background There is a growing body of nuclear contrast agents that are repurposed for fluorescence-guided surgery. New contrast agents are obtained by substituting the radioactive tag with, or adding a fluorescent cyanine to the molecular structure of antibodies or peptides. This enables intra-operative fluorescent detection of cancerous tissue, leading to more complete tumor resection. However, these fluorescent cyanines can have a remarkable influence on pharmacokinetics and tumor uptake, especially when labeled to smaller targeting vectors such as peptides. Here we demonstrate the effect of cyanine-mediated dead cell-binding of Ac-Lys0(IRDye800CW)-Tyr3-octreotate (800CW-TATE) and how this can be used as an advantage for fluorescence-guided surgery. Results Binding of 800CW-TATE could be blocked with DOTA0-Tyr3-octreotate (DOTA-TATE) on cultured SSTR2-positive U2OS cells and was absent in SSTR2 negative U2OS cells. However, strong binding was observed to dead cells, which could not be blocked with DOTA-TATE and was also present in dead SSTR2 negative cells. No SSTR2-mediated binding was observed in frozen tumor sections, possibly due to disruption of the cells in the process of sectioning the tissue before exposure to the contrast agent. DOTA-TATE blocking resulted in an incomplete reduction of 61.5 ± 5.8% fluorescence uptake by NCI-H69-tumors in mice. Near-infrared imaging and dead cell staining on paraffin sections from resected tumors revealed that fluorescence uptake persisted in necrotic regions upon blocking with DOTA-TATE. Conclusion This study shows that labeling peptides with cyanines can result in dead cell binding. This does not hamper the ultimate purpose of fluorescence-guided surgery, as necrotic tissue appears in most solid tumors. Hence, the necrosis binding can increase the overall tumor uptake. Moreover, necrotic tissue should be removed as much as possible: it cannot be salvaged, causes inflammation, and is tumorigenic. However, when performing binding experiments to cells with disrupted membrane integrity, which is routinely done with nuclear probes, this dead cell-binding can resemble non-specific binding. This study will benefit the development of fluorescent contrast agents.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Necrosis binding of Ac-Lys0(IRDye800CW)-Tyr3-octreotate: a consequence from cyanine-labeling of small molecules

et al. 2021

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Targeted optical fluorescence imaging: a meta-narrative review and future perspectives

Schouw

Huisman

Janssen

et al. 2021

Eur J Nucl Med Mol Imaging

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Purpose The aim of this review is to give an overview of the current status of targeted optical fluorescence imaging in the field of oncology, cardiovascular, infectious and inflammatory diseases to further promote clinical translation. Methods A meta-narrative approach was taken to systematically describe the relevant literature. Consecutively, each field was assigned a developmental stage regarding the clinical implementation of optical fluorescence imaging. Results Optical fluorescence imaging is leaning towards clinical implementation in gastrointestinal and head and neck cancers, closely followed by pulmonary, neuro, breast and gynaecological oncology. In cardiovascular and infectious disease, optical imaging is in a less advanced/proof of concept stage. Conclusion Targeted optical fluorescence imaging is rapidly evolving and expanding into the clinic, especially in the field of oncology. However, the imaging modality still has to overcome some major challenges before it can be part of the standard of care in the clinic, such as the provision of pivotal trial data. Intensive multidisciplinary (pre-)clinical joined forces are essential to overcome the delivery of such compelling phase III registration trial data and subsequent regulatory approval and reimbursement hurdles to advance clinical implementation of targeted optical fluorescence imaging as part of standard practice.

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Fluorescent risedronate analogue 800CW-pRIS improves tooth extraction-associated abnormal wound healing in zoledronate-treated mice

et al. 2022

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Background Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare but serious side effect of nitrogen-containing bisphosphonate drugs (N-BPs) frequently prescribed to reduce skeletal-related events in bone malignancies and osteoporosis. BRONJ is associated with abnormal oral wound healing after dentoalveolar surgery and tooth extraction. We previously found that N-BP chemisorbed to bone mineral hydroxyapatite was dissociated by secondary applied N-BP. This study investigated the effect of the surface equilibrium-based removal of N-BP from jawbone on tooth extraction wound healing of zoledronate (ZOL)-treated mice. Methods A pharmacologically inactive N-BP derivative (the 4-pyridyl isomer of risedronate equipped with a near-infrared 800CW fluorescent imaging dye, 800CW-pRIS) was designed and synthesized. 800CW-pRIS was intra-orally injected or topically applied in a deformable nano-scale vesicle formulation (DNV) to the palatal tissue of mice pretreated with ZOL, a potent N-BP. The female C56BL6/J mice were subjected to maxillary molar extraction and oral wound healing was compared for 800CW-pRIS/ZOL, ZOL and untreated control groups. Results 800CW-pRIS is confirmed to be inactive in inhibiting prenylation in cultured osteoclasts while retaining high affinity for hydroxyapatite. ZOL-injected mice exhibit delayed tooth extraction wound healing with osteonecrosis relative to the untreated controls. 800CW-pRIS applied topically to the jaw one week before tooth extraction significantly reduces gingival oral barrier inflammation, improves extraction socket bone regeneration, and prevents development of osteonecrosis in ZOL-injected mice. Conclusions Topical pre-treatment with 800CW-RIS in DNV is a promising approach to prevent the complication of abnormal oral wound healing associated with BRONJ while retaining the anti-resorptive benefit of legacy N-BP in appendicular or vertebrate bones.

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Evaluation of Ac-Lys0(IRDye800CW)Tyr3-octreotate as a novel tracer for SSTR2-targeted molecular fluorescence guided surgery in meningioma

Cited by 7 publications

References 37 publications

Necrosis binding of Ac-Lys0(IRDye800CW)-Tyr3-octreotate: a consequence from cyanine-labeling of small molecules

Necrosis binding of Ac-Lys0(IRDye800CW)-Tyr3-octreotate: a consequence from cyanine-labeling of small molecules

Targeted optical fluorescence imaging: a meta-narrative review and future perspectives

Fluorescent risedronate analogue 800CW-pRIS improves tooth extraction-associated abnormal wound healing in zoledronate-treated mice

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