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. 2018 Nov 29;23(12):3138.
doi: 10.3390/molecules23123138.

Biodistribution and Tumor Uptake of 67Ga-Nimotuzumab in a Malignant Pleural Mesothelioma Xenograft

Vanessa Izquierdo-Sánchez  1   2 , Saé Muñiz-Hernández  3 , Héctor Vázquez-Becerra  4   5 , Judith Pacheco-Yepez  6 , Mario E Romero-Piña  7 , Oscar Arrieta  8   9 , Luis Alberto Medina  10   11
Affiliations

Biodistribution and Tumor Uptake of 67Ga-Nimotuzumab in a Malignant Pleural Mesothelioma Xenograft

Vanessa Izquierdo-Sánchez et al. Molecules. .

Abstract

Malignant pleural mesothelioma (MPM) is the most common tumor of the pulmonary pleura. It is a rare and aggressive malignancy, generally associated with continuous occupational exposure to asbestos. Only a multimodal-approach to treatment, based on surgical resection, chemotherapy and/or radiation, has shown some benefits. However, the survival rate remains low. Nimotuzumab (h-R3), an anti-EGFR (epidermal growth factor receptor) humanized antibody, is proposed as a promising agent for the treatment of MPM. The aim of this research was to implement a procedure for nimotuzumab radiolabeling to evaluate its biodistribution and affinity for EGF (epidermal growth factor) receptors present in a mesothelioma xenograft. Nimotuzumab was radiolabeled with 67Ga; radiolabel efficiency, radiochemical purity, serum stability, and biodistribution were evaluated. Biodistribution and tumor uptake imaging studies by microSPECT/CT in mesothelioma xenografts revealed constant nimotuzumab uptake at the tumor site during the first 48 h after drug administration. In vivo studies using MPM xenografts showed a significant uptake of this radioimmunoconjugate, which illustrates its potential as a biomarker that could promote its theranostic use in patients with MPM.

Keywords: biomarkers; malignant pleural mesothelioma; molecular imaging; nimotuzumab; radioimmunoconjugates.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
SDS-PAGE. Molecular weight size marker, (a) Nimotuzumab, (b) conjugate diethylenetriaminepentaacetic acid (DTPA)-nimotuzumab, (c) residual DTPA after purification, (d) DTPA, (f) nimotuzumab semi-reduction conditions.
Figure 2
Figure 2
Left: The 18FDG PET/CT image denotes the metabolic activity of a mesothelioma xenograft. Images a–d: 67Ga-nimotuzumab SPECT/CT shows nimotuzumab uptake in the tumor at 1, 12, 24, and 48 h post-injection. All images show transversal projections based on the tumor position of the same animal at different times.
Figure 3
Figure 3
Representative transversal projection of each animal illustrating the tumor uptake of 67Ga-nimotuzumab at 24 h post-injection. Arrows point to tumor location.
Figure 4
Figure 4
Representative SPECT/CT 3D-images showing the differences in biodistribution and uptake in mesothelioma xenografts at 24 h post-injection for: (A) 67Ga (control group) and (B) 67Ga-nimotuzumab.
Figure 5
Figure 5
Biodistribution profile of 67Ga-nimotuzumab in the tumor and organs of interest at 48 h. Values represent the mean ±SEM (n = 3).
See this image and copyright information in PMC

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