Radioimmunolocalisation in breast cancer using the gene product of c-erbB2 as the target antigen

Abstract

Summary Lymph node status is still the single most important prognostic factor in breast cancer. Axillary surgery remains the only reliable means of providing this information. This pilot study evaluates using a highly specific radiolabelled monoclonal antibody to provide equivalent infornation by a non-invasive technique.After optimisation of labelling conditions, our first antibody, ICR12 (against the gene product of c-erbB-2) was evaluated in a mouse model system. Twenty-four hours post i.v. injection the mice were killed and their organs, blood and tumours harvested for counting. Tumour localisation was four times greater than that into normal tissues, reaching 20% injected dose per gram of tumour.Eight patients have had this Tc99m-ICR12. Patient selection was by immunocytochemical staining of fine needle aspirates from the patient's own breast cancer. After intravenous administration of the immunoconjugate, tomographic images were obtained at 24h. These results were compared to the subsequent histopathological examinations. Three patients acted as normal controls, one patient was negative due to inappropriate sampling, and two patients had strong membrane staining and provided excellent tumour localisation to both breast primary and regional node metastases. A further two patients only had moderate antigen expression on staining and did not localise well.The good performance of this radiolabelled antibody with patients that strongly stain for the antigen encourages the development of this system as both a method of staging breast cancer and a potential means of immunotherapy in this subgroup of patients.

Development and Characterization of Clinical-Grade 89Zr-Trastuzumab for HER2/neu ImmunoPET Imaging

“…Tumor uptake of ICR12 was further increased, to 20 %ID/g, with residualizing isotopes (28,29). Similar to what we observed in the present study, tumor uptake of ICR12 was not influenced by the protein dose, but the T/B ratio decreased with an increasing amount of protein (30).…”

“…In the early 1990s, the rat antibody 99m Tc-ICR12 was administered to 8 breast cancer patients. Tomographic images were obtained at 24 h. The study indicated that 99m Tc-ICR12 could be used for the imaging of HER2/neu overexpression (29), but no further clinical results with this rodent antibody have been published. In a preliminary report, Behr et al suggested that 111 In-trastuzumab could predict the therapeutic efficacy of trastuzumab in 20 patients with HER2/neu-overexpressing metastatic breast cancer (36).…”

Biodistribution of 89Zr-trastuzumab and PET Imaging of HER2-Positive Lesions in Patients With Metastatic Breast Cancer

“…This SPECT study suggested that 99m Tc‐ICR12 could be used for the imaging of HER2‐positive disease, although no further clinical results involving this antibody have been made available. 23 Currently, clinical studies with 111 In‐ and 64 Cu‐trastuzumab and with 68 Ga‐trastuzumab F(ab′) 2 fragments are at the stage of patient recruitment. 24 , 25 , 26 These studies will give insight into the possibility of using shorter‐lived isotopes (such as 64 Cu) for imaging with intact antibodies and will provide the first clinical results with the smaller HER2‐directed F(ab′) 2 fragments.…”

Growth Factor Receptors in Breast Cancer: Potential for Therapeutic Intervention

“…These have shown the ability to image tumors in experimental animals and in humans [90,91]. The therapeutic application of radiolabelled antibodies to this and other types of cancer may depend on the attachment of isotopes of sufficient specific activity and suitable decay pathlength.…”