Abstract
The oncogene HER2 is an important molecular target in oncology because it is associated with aggressive disease and the worst prognosis. The development of non-invasive imaging techniques and target therapies using monoclonal antibodies is a rapidly developing field. Thus, this work proposes the study of the radioimmunotheranostic pair, [111In]In-DTPA-trastuzumab and [177Lu]Lu-DOTA-trastuzumab, evaluating the influence of the chelating agents and radionuclides on the biological properties of the radioimmunoconjugates (RICs). The trastuzumab was immunoconjugated with the chelators DTPA and DOTA and radiolabeled with [111In]InCl3 and [177Lu]LuCl3, respectively. The stability of the RICs was evaluated in serum, and the immunoreactive and internalization fractions were determined in SK-BR-3 breast cancer cells. The in vivo pharmacokinetics and dosimetry quantification and the ex vivo biodistribution were performed in normal and SK-BR-3 tumor-bearing mice. The data showed that there was no influence of the chelating agents and radionuclides on the immunoreactive and internalization fractions of RICs. In contrast, they influenced the stability of RICs in serum, as well as the pharmacokinetics, dosimetry and biodistribution profiles. Therefore, the results showed that the nature of the chelating agent and radionuclide could influence the biological properties of the radioimmunotheranostic pair.
Highlights
Personalized oncology is based on evidence and offers more assertive decisions for each patient, leading to successful results and reduced healthcare costs
Previous MALDI–TOF studies revealed an average number of 6–7 molecules of p-SCN-Bn-DTPA and 8–9 molecules of DOTA-NHS-ester coupled to trastuzumab for a 1:20 M ratio [25]
The results showed 97 and 98% of the preserved immunoreactivity for the [111 In]In-DTPA-trastuzumab and [177 Lu]Lu-DOTA-trastuzumab, respectively
Summary
Personalized oncology is based on evidence and offers more assertive decisions for each patient, leading to successful results and reduced healthcare costs. It involves genomic analysis, target-specific drugs, treatment and diagnosis by molecular imaging. HER2 is an important molecular target in oncology because it is related to more aggressive tumor development in patients [2,3,4]. Breast cancer is a tumor type that overexpresses the HER2 oncogene in approximately 20% to 30% of cases; this expression is associated with the worst prognosis [3,5,6]. The available diagnostic methods are invasive and may present inconsistent results due to intratumoral heterogeneity, and the sample size of the biopsied tumor may not represent the whole tumor expression, as well as the possibility of promoting metastatic lesions by repeated biopsies [2]
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