A new microdispersed albumin derivative potentially useful for radio-guided surgery of occult breast cancer lesions

• Published in: Scientific reports Vol. 9; no. 1; p. 5623
• Main Authors: Caviglioli, Gabriele, Chinol, Marco, Baldassari, Sara, Garaboldi, Lucia, Zuccari, Guendalina, Petretto, Andrea, Drava, Giuliana, Sinico, Chiara, Paganelli, Giovanni
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.04.2019; Nature Publishing Group
• Subjects: 59/78; 692/4028/546; 692/4028/67/1347; Albumin; Albumins - administration & dosage; Animals; Breast cancer; Breast Neoplasms - diagnostic imaging; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Computed tomography; Female; Half-life; Heterocyclic Compounds - administration & dosage; Heterocyclic Compounds - chemistry; Heterocyclic Compounds - pharmacology; Humanities and Social Sciences; Isothiocyanates - administration & dosage; Isothiocyanates - chemistry; Isothiocyanates - pharmacology; Localization; Mammary gland; Microspheres; multidisciplinary; Nuclear medicine; Oncology; Pharmaceuticals; Powder; Proteins; Radioactivity; Radioisotopes; Radionuclide Imaging - methods; Radiopharmaceuticals; Rats; Science; Science (multidisciplinary); Sentinel Lymph Node Biopsy - methods; Surgeons; Surgery; Surgery, Computer-Assisted - methods; Technetium; Technetium Tc 99m Aggregated Albumin - administration & dosage; Technetium Tc 99m Aggregated Albumin - chemistry; Technetium Tc 99m Aggregated Albumin - pharmacology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-42014-2

This paper describes a new nuclear imaging agent, 2-(4-isothiocyanatobenzyl)−1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid of human albumin (HAC), potentially suitable for application in the Radio-guided Occult Lesion Localization (ROLL) of non-palpable mammalian cancerous lesions, as a tool to overtake the short radio-signal half-life of the technetium-99m based radiopharmaceutical currently used. This conjugate is a microsized powder aggregate, water-insoluble between pH 3 and 8.5, obtained by conjugating the protein with the macrocyclic chelating agent DOTA through a one-pot reaction in aqueous medium. The product has been fully characterized and is stable to the thermal conditions adopted for labeling; after radiolabeling with longer half-life radionuclides such as 177 Lu or 111 In, it has shown radiochemical purity (RCP) >90% and resulted stable when stored in saline or plasma for 6 days at 37 °C. A μPET/CT study, performed in vivo on adult female rats, showed that the radioactivity of HAC labeled with 64 Cu remained located in the mammary glands for at least 40 h, without diffusion or drainage in healthy tissues or in the lymphatic circulation. This new imaging agent might make the ROLL procedure more accessible, safe and flexible, promoting a significant time and cost reduction of this intervention. Moreover, HAC might also be used in other radio-guided surgical procedures in oncology.