Indium-111–labeled Girentuximab ImmunoSPECT as a Diagnostic Tool in Clear Cell Renal Cell Carcinoma

Muselaers, Stijn; Boerman, Otto C.; Oosterwijk, Egbert; Langenhuijsen, J.F.; Oyen, Wim J.G.; Mulders, Peter F.A.

doi:10.1016/j.eururo.2013.02.022

Cited by 70 publications

(55 citation statements)

References 14 publications

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“…This study confirmed previous studies showing that clear cell RCC lesions can be visualized with 111 In-girentuximab imaging (17,19). High and specific uptake was seen in tumor lesions in all patients with clear cell RCC.…”

Section: Discussionsupporting

confidence: 80%

Tyrosine Kinase Inhibitor Sorafenib Decreases ¹¹¹In-Girentuximab Uptake in Patients with Clear Cell Renal Cell Carcinoma

Muselaers¹,

Stillebroer

Desar³

et al. 2014

J Nucl Med

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Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of metastatic clear cell renal cell carcinoma (RCC). Although TKIs have demonstrated good clinical efficacy, the lack of complete responses, the chronic nature of the treatment, and the side effects are clear disadvantages. An interesting new approach in the treatment of clear cell RCC is antibody-mediated therapy with the chimeric anti-carbonic anhydrase IX (CAIX) antibody girentuximab (cG250). As the results of several girentuximab trials become available, the question arises of whether TKI treatment can be combined with girentuximabbased therapy. In this study, we assessed the effect of the widely used TKI sorafenib on the tumor-targeting potential of 111 In-labeled girentuximab. Methods: 111 In-girentuximab imaging was performed on 15 patients suspected of having a renal malignancy, with surgery being part of their treatment plan. Of these, 10 patients were treated in a neoadjuvant setting with sorafenib (400 mg orally twice daily). Five patients received treatment during 1 wk, and 5 patients received treatment during 4 wk. In both sorafenib-treated groups, baseline and posttreatment tumor targeting of 111 In-girentuximab were compared. Surgery was performed 3 d after the last image acquisition. Five additional patients were included as a control group and had only a single 111 In-girentuximab injection and scintigraphy without any treatment. Distribution of 111 In-girentuximab was determined scintigraphically ex vivo in a 1-cm lamella of the resected tumorous kidney. Expression of CAIX and of the vascular marker CD31 was determined immunohistochemically on specimens of both tumor and normal kidney tissue. Results: Treatment with sorafenib resulted in a marked decrease of 111 In-girentuximab uptake in the tumor in clear cell RCC patients, especially in the group treated for 4 wk (mean change in both sorafenib-treated groups, 238.4%; range, 19.1% to 279.4%). Immunohistochemical analysis showed markedly reduced CD31 expression and vessel density in the sorafenib-treated groups but no differences in CAIX expression between the sorafenib-treated groups and the nontreated patients. Conclusion: Treatment with sorafenib resulted in a treatment duration-dependent significantly decreased uptake of 111 In-girentumab in clear cell RCC lesions. These results indicate that the efficacy of antibody-mediated treatment or diagnosis modalities is hampered by TKI treatment.

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Section: Discussionsupporting

confidence: 80%

Tyrosine Kinase Inhibitor Sorafenib Decreases ¹¹¹In-Girentuximab Uptake in Patients with Clear Cell Renal Cell Carcinoma

Muselaers¹,

Stillebroer

Desar³

et al. 2014

J Nucl Med

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“…The high liver uptake of 111 In-labetuzumabIRDye800CW and the prolonged retention of 111 In in the liver may limit the role of the dual-labeled agent in the detection of micrometastases in or near the liver. Clinical trials with 111 In-labeled antibodies in other tumor types have shown that imaging of liver metastases with 111 In-labeled monoclonal antibodies is feasible (28,29). However, the addition of a fluorescent label (IRDye800CW) may reduce tumor-to-liver contrast because of the enhanced uptake in the liver (30).…”

Section: Discussionmentioning

confidence: 99%

Detection of Micrometastases Using SPECT/Fluorescence Dual-Modality Imaging in a CEA-Expressing Tumor Model

et al. 2017

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Intraoperative dual-modality imaging can help the surgeon distinguish tumor from normal tissue. This technique may prove particularly valuable if small tumors need to be removed that are difficult to detect with the naked eye. The humanized anticarcinoembryonic antigen (anti-CEA) monoclonal antibody, labetuzumab, can be used as a tumor-targeting agent in colorectal cancer, since CEA is overexpressed in approximately 95% of colorectal cancer. Dual-labeled labetuzumab, labeled with both a near-infrared fluorescent dye (IRDye800CW) and a radioactive label ( 111 In), can be used as a tracer for dual-modality imaging. This study aimed to assess whether dualmodality imaging using 111 In-diethylenetriaminepentaacetic acid (DTPA)-labetuzumab-IRDye800CW can detect pulmonary micrometastases in a mouse model. Methods: Pulmonary GW-39 human colonic carcinoma microcolonies were induced in athymic BALB/c mice by intravenous injection of 100 mL of a GW-39 cell suspension. After 1, 2, 3, and 4 wk of tumor growth, dual-modality imaging was performed 3 d after intravenous injection of 111 In-DTPA-labetuzumabIRDye800CW (10 mg, 25 MBq). Small-animal SPECT images and optical images were acquired, and image-guided surgery was performed. Finally, the biodistribution of the dual-labeled tracer was determined. Formalin-fixed sections of the lungs were analyzed using fluorescence imaging, autoradiography, and immunohistochemistry. Results: Submillimeter pulmonary tumor colonies could be visualized with both small-animal SPECT and fluorescence imaging from the first week of tumor growth, before they became visible to the naked eye. Furthermore, dual-modality imaging could be used to guide resection of tumors. Mean uptake (percentage injected dose per gram) of the dual-labeled tracer in tumors was 17.2 6 5.4 and 16.5 6 4.4 at weeks 3 and 4, respectively. Immunohistochemical analysis of the tumorous lungs showed that the distribution of the radioactive and fluorescent signal colocalized with CEA-expressing tumors. Conclusion: Dualmodality imaging after injection of 111 In-labetuzumab-IRDye800CW can be used to detect submillimeter CEA-expressing pulmonary tumors before they become visible to the naked eye, supporting the added value of this technique in the resection of small tumors.

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“…Because of its long half-life (59.4 d) and less favorable g characteristics (g energy 5 35 keV), 125 I is not suitable for SPECT imaging in the clinical setting. Labeling of girentuximab-IRDye800CW with 124 I or with the residualizing radiometal 111 In by use of the chelator DTPA could enable preoperative molecular imaging in patients with ccRCC tumors and thus enable both pre-and perioperative imaging of ccRCC tumors (24)(25)(26)(27). Recently, Divgi et al (26) assessed the accuracy of 124 I-girentuximab PET/CT in a large cohort of patients with a primary renal mass scheduled for surgery.…”

Section: Discussionmentioning

confidence: 99%

Optical Imaging of Renal Cell Carcinoma with Anti–Carbonic Anhydrase IX Monoclonal Antibody Girentuximab

et al. 2014

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Indium-111–labeled Girentuximab ImmunoSPECT as a Diagnostic Tool in Clear Cell Renal Cell Carcinoma

Cited by 70 publications

References 14 publications

Tyrosine Kinase Inhibitor Sorafenib Decreases ¹¹¹In-Girentuximab Uptake in Patients with Clear Cell Renal Cell Carcinoma

Tyrosine Kinase Inhibitor Sorafenib Decreases ¹¹¹In-Girentuximab Uptake in Patients with Clear Cell Renal Cell Carcinoma

Detection of Micrometastases Using SPECT/Fluorescence Dual-Modality Imaging in a CEA-Expressing Tumor Model

Optical Imaging of Renal Cell Carcinoma with Anti–Carbonic Anhydrase IX Monoclonal Antibody Girentuximab

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Indium-111–labeled Girentuximab ImmunoSPECT as a Diagnostic Tool in Clear Cell Renal Cell Carcinoma

Cited by 70 publications

References 14 publications

Tyrosine Kinase Inhibitor Sorafenib Decreases 111In-Girentuximab Uptake in Patients with Clear Cell Renal Cell Carcinoma

Tyrosine Kinase Inhibitor Sorafenib Decreases 111In-Girentuximab Uptake in Patients with Clear Cell Renal Cell Carcinoma

Detection of Micrometastases Using SPECT/Fluorescence Dual-Modality Imaging in a CEA-Expressing Tumor Model

Optical Imaging of Renal Cell Carcinoma with Anti–Carbonic Anhydrase IX Monoclonal Antibody Girentuximab

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Tyrosine Kinase Inhibitor Sorafenib Decreases ¹¹¹In-Girentuximab Uptake in Patients with Clear Cell Renal Cell Carcinoma

Tyrosine Kinase Inhibitor Sorafenib Decreases ¹¹¹In-Girentuximab Uptake in Patients with Clear Cell Renal Cell Carcinoma