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

Gabriele Caviglioli,Sara Baldassari,Lucia Garaboldi,Andrea Petretto,Giuliana Drava,Guendalina Zuccari,Marco Chinol,Chiara Sinico,Giovanni Paganelli

doi:10.1038/s41598-019-42014-2

Abstract

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 177Lu or 111In, 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 64Cu 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.

Highlights

This paper describes a new nuclear imaging agent, 2-(4-isothiocyanatobenzyl)−1,4,7,10tetraazacyclododecane-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
That form stable and kinetically inert complexes with di- and trivalent cations[16], we selected 2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bn-DOTA), for its easy reaction with nucleophilic sites, which are present on the amino acid lateral chains of HA, under mild conditions in aqueous media[17]
The formation of the MAA is based on the cross-linking between amines and carboxylic groups present on the lateral chains of the protein, free amino groups are likely to be minimally present on the surface of the MAA

Summary

Introduction

This paper describes a new nuclear imaging agent, 2-(4-isothiocyanatobenzyl)−1,4,7,10tetraazacyclododecane-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. Different techniques have been developed with this purpose, including carbon marking and wire-guided localization, but the efficiency, safety and the economic benefits of ROLL (Radio-guided Occult Lesion Localization) have been confirmed by several meta-analyses[3,4,5,6,7]

Methods

Results

Conclusion