Perspectives on the phase 0 clinical trial of microdose administration of ABY-029 for fluorescence guided surgery: stability testing

SummaryOptical imaging has long been considered a method for histological or microscopic investigations. Over the last 15 years, however, this method was applied for preclinical molecular imaging and, just recently, was also able to show its principal potential for clinical applications (e.g. fluorescence-guided surgery). Reviewing the development and preclinical evaluation of new fluorescent dyes and target-specific dye conjugates, these often show characteristic patterns of their routes of excretion and biodistribution, which could also be interesting for the development and optimization of radiopharmaceuticals. Especially ionic charges show a great influence on biodistribution and netcharge and charge-distribution on a conjugate often determines unspecific binding or background signals in liver, kidney or intestine, and other organs.Learning from fluorescent probe behaviour in vivo and translating this knowledge to radio-pharmaceuticals might be useful to further optimize emerging and existing radiopharmaceuticals with respect to their biodistribution and thereby availability for binding to their targets.

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Fluorescence-guided Surgery Using cRGD-ZW800-1 in Oral Cancer

Case Medical Research ◽

10.31525/ct1-nct04191460 ◽

2019 ◽

Author(s):

Keyword(s):

Oral Cancer ◽

Guided Surgery ◽

Fluorescence Guided Surgery

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Unexpected Binding of Tozuleristide “Tumor Paint” to Cerebral Vascular Malformations: A Potentially Novel Application of Fluorescence-Guided Surgery

Neurosurgery ◽

10.1093/neuros/nyab106 ◽

2021 ◽

Author(s):

Andrew J Kobets ◽

David Nauen ◽

Amy Lee ◽

Alan R Cohen

Keyword(s):

Near Infrared ◽

Vascular Malformations ◽

Cns Tumors ◽

Matrix Metalloproteinase 2 ◽

Cerebrovascular Lesions ◽

Cavernous Malformations ◽

Guided Surgery ◽

Fluorescence Guided Surgery ◽

Cerebral Vascular Malformations ◽

Cerebral Vascular

Abstract BACKGROUND Fluorescence-guided surgery (FGS) is under investigation as a means to improve the extent of resection for primary central nervous system (CNS) tumors. Tozuleristide, known also as “Tumor Paint,” is an investigational tumor-targeting agent covalently conjugated to a derivative of the fluorescent dye indocyanine green. OBJECTIVE To report the finding of avid intraoperative fluorescence of tozuleristide on cerebral vascular malformations. METHODS Our institution is participating in a phase 2/3 study of intraoperative near-infrared fluorescence detection of pediatric primary CNS tumors in patients receiving intravenous tozuleristide and imaged with the Canvas system. Our site enrolled 2 patients with intracranial lesions, suspected preoperatively of possibly being gliomas that proved to be cavernous vascular malformations after resection. RESULTS Each lesion had a dark blue mulberry appearance and each fluoresced avidly with tozuleristide. Each was completely resected, and the patients recovered without deficit. Pathological assessment showed cavernous angioma for both cases. Tozuleristide fluorescence is postulated to result from binding to matrix metalloproteinase-2 and annexin A2, and literature review demonstrates expression of both these ligands on multiple cerebrovascular lesions, including cavernous malformations. CONCLUSION This finding deserves further investigation to determine if tozuleristide “Tumor Paint” may have a wider role in the identification of non-neoplastic intracranial pathologies.

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