Preliminary biological evaluation of 123I-labelled anti-CD30-LDM in CD30-positive lymphomas murine models

Abstract

Overexpression of CD30 has been reported on the surface of some T-cell lymphomas, especially on Hodgkin's lymphoma (HL) and anaplastic large cell lymphoma (ALCL). CD30 targeted immunotherapy has good clinical therapy response. We have produced a novel antibody drug conjugates (ADCs)-anti-CD30-LDM, which shows attractive tumour-targeting capability and extremely potent antitumor efficacy. To further investigate biological characteristics and promote clinical translation of anti-CD30-LDM, we constructed a radiolabeled 123 I-anti-CD30-LDM to evaluate the biodistribution characteristics. The anti-CD30-LDM was radioiodinated by the Iodogen method. The radiochemical purity of 123 I-anti-CD30-LDM was more over 98%, and the specific activity of 240.5 MBq/mg. The stability and the specificity of 123 I-anti-CD30-LDM were evaluated in vitro. Cellular binding assays were used to evaluate the binding capabilities in CD30-positive Karpas299 cells and CD30-negative Raji cells. B-NDG mice bearing Karpas 299 and Raji xenografts were used for in vivo biodistribution studies. Our results demonstrated that anti-CD30-LDM as an ideal ADC targeted to CD30, which was labelled easily with 123 I and obtained the sufficient yields. The 123 I-anti-CD30-LDM preserved specific binding to CD30 in vitro and uptake in tumour xenografts in B-NDG mice. These results are encouraging for anti-CD30-LDM as a promising clinical translational candidate for various CD30 positive lymphomas and other diseases.

Monitoring In Vivo Performances of Protein–Drug Conjugates Using Site-Selective Dual Radiolabeling and Ex Vivo Digital Imaging

“…Although the use of radiolabeling is undoubtedly an efficient way to address the plasma and tissue ADC profiles with a high detection threshold, it suffers from two main limitations. In almost all the studies reported so far, the radioisotopes are incorporated either into the drug or the protein, and therefore, the simultaneous in vivo monitoring of both entities is not straightforwardly achieved. − Furthermore, the radiolabeling of monoclonal antibody systematically implies a random conjugation of the radioactive species within the protein core, which could lead to potential alterations of the ADC binding and biodistribution properties. − …”

Radiotheranostic Agents in Hematological Malignancies

“…To study its biodistribution, this conjugate was radioiodinated. After injection in CD30 + lymphoma-bearing mice, the retention of the tracer in tumor tissues was twice as high in CD30 + compared to CD30-negative tumors ( 142 ).…”

Antibody–Drug Conjugates for Cancer Therapy

“…Anti-CD30-LDM alone or combination with crizotinib has shown significant anti-tumor activity in a CD30+/ALK+ anaplastic large-cell lymphoma model [ 174 ]. Anti-CD30-LDM was radiolabeled with 123 I and demonstrated strong binding capabilities in CD30-positive cells, and a biodistribution study showed a 2-fold higher tumor uptake in CD30+ versus CD30- tumors (4.98 ± 0.99%ID/g vs. 2.75 ± 0.47%ID/g, respectively) [ 175 ]. These findings support the potential use of 123 I-anti-CD30-LDM as a companion diagnostic in the further clinical development of anti-CD30-LDM.…”