Phase I study to assess safety, biodistribution and radiation dosimetry for 89Zr-girentuximab in patients with renal cell carcinoma

Abstract

Purpose In this phase I study, we evaluated the safety, biodistribution and dosimetry of [89Zr]Zr-DFO-girentuximab (89Zr-girentuximab) PET/CT imaging in patients with suspicion of clear cell renal cell carcinoma (ccRCC). Methods Ten eligible patients received an intravenous administration of 37 MBq (± 10%) of 89Zr-girentuximab at mass doses of 5 mg or 10 mg. Safety was evaluated according to the NCI CTCAE (version 4.03). Biodistribution and normal organ dosimetry was performed based on PET/CT images acquired at 0.5, 4, 24, 72 and 168 h post-administration. Additionally, tumour dosimetry was performed in patients with confirmed ccRCC and visible tumour uptake on PET/CT imaging. Results 89Zr-girentuximab was administered in ten patients as per protocol. No treatment-related adverse events ≥ grade 3 were reported. 89Zr-girentuximab imaging allowed successful differentiation between ccRCC and non-ccRCC lesions in all patients, as confirmed with histological data. Dosimetry analysis using OLINDA/EXM 2.1 showed that the organs receiving the highest doses (mean ± SD) were the liver (1.86 ± 0.40 mGy/MBq), the kidneys (1.50 ± 0.22 mGy/MBq) and the heart wall (1.45 ± 0.19 mGy/MBq), with a mean whole body effective dose of 0.57 ± 0.08 mSv/MBq. Tumour dosimetry was performed in the 6 patients with histologically confirmed ccRCC resulting in a median tumour-absorbed dose of 4.03 mGy/MBq (range 1.90–11.6 mGy/MBq). Conclusions This study demonstrates that 89Zr-girentuximab is safe and well tolerated for the administered activities and mass doses and allows quantitative assessment of 89Zr-girentuximab PET/CT imaging in patients with suspicion of ccRCC. Trial registration NCT03556046—14th of June, 2018

Advances in Imaging-Based Biomarkers in Renal Cell Carcinoma: A Critical Analysis of the Current Literature

“…Its preliminary results were reported recently, and exceed the predetermined sensitivity and specificity study targets, with the imaging agent delivering 86% sensitivity and 87% specificity [46]. The phase I study showed in all ten cases a good toxicity profile, and was able to differentiate between clear-cell RCC and non-clear-cell RCC renal mass [47]. This technology is also being examined for diagnostic and therapeutic purposes in the STARLITE 2 Phase II study which evaluates the efficacy of Lu177 conjugated to girentuximab + nivolumab (anti-PD-1) systemic therapy.…”

Advances in PET and MRI imaging of tumor hypoxia

“…The biodistribution is similar to that of other [ 89 Zr]-mAb with a slow clearance from liver, heart, kidney and blood pool. The uptake from renal cell carninoma (assumed to be hypoxic) is rather slow in the clinical trial performed by Merkx et al ( 156 ).…”

Radiolabeled Antibodies for Cancer Imaging and Therapy

“…CAIX is overexpressed in clear-cell renal-cell tumors (ccRCC) due to a mutation in the Von Hippel-Lindau protein [41]. A number of biodistribution studies have evaluated 89 Zr-labeled girentuximab, an anti-CAIX monoclonal antibody [42][43][44]. These studies have shown 89 Zr-girentuximab was safe and allowed differentiation between ccRCC and non-ccRCC lesions, enabling early detection of tumor recurrence and inform clinical decision making (Figure 2).…”