Intraoperative Dual-modality Imaging in Renal Cell Carcinoma

Phase 1

Interventions: Drug: Indium-111-DOTA-Girentuximab-IRDye800CW
Radiation: SPECT/CT
Procedure: Intraoperative dual-modality imaging

Brief Summary: Intraoperative tumor localization and resection can be enhanced using intraoperative fluorescence imaging and radiodetection. Girentuximab specifically recognizes carbonic anhydrase IX expressed on \> 95% of renal cell carcinoma (RCC). Therefore Indium-111-DOTA-girentuximab-IRDye800CW is a perfect dual-labeled antibody for dual-modality image-guided surgery in RCC.

The aim of this study is to assess the feasibility and safety of intraoperative dual-modality imaging with Indium-111-DOTA-girentuximab-IRDye800CW in renal cell carcinoma patients.

Detailed Description: In oncologic surgery complete tumor resection is important for treatment outcome and patient survival. Intraoperative tumor localization and resection can be enhanced using intraoperative imaging techniques (e.g. targeted radioguided or fluorescence guided surgery). A powerful synergy can be achieved by combining radiotracers (e.g. Indium-111) and optical tracers (e.g. IRDye 800CW) conjugated to an antibody against a tumor-associated antigen. Girentuximab specifically recognizes carbonic anhydrase IX expressed on \> 95% of renal cell carcinoma (RCC). Therefore Indium-111-DOTA-girentuximab-IRDye800CW is a perfect dual-labeled antibody for dual-modality image-guided surgery in RCC. The concept has been shown in preclinical studies with mice and the investigators will translate this to the clinic.

Eligible patients with renal cell carcinoma scheduled for (partial) nephrectomy will receive dual-labeled girentuximab 7 days before surgery. At day 4 or 5 a SPECT/CT of the abdomen will be obtained. Surgery at day 7 will be extended with the use of a near-infrared fluorescence camera and a gamma probe.

The aim of this study is to assess the feasibility and safety of intraoperative dual-modality imaging with Indium-111-DOTA-girentuximab-IRDye800CW in renal cell carcinoma.

Recruitment & Eligibility

Inclusion Criteria

Clinical diagnosis of clear cell renal cell carcinoma planned for surgery, (partial) nephrectomy
Performance status: Karnofsky 70 %
Being fit for surgery
Minimum age 18 years
Signed informed consent

Exclusion Criteria

A known subtype other than clear cell RCC
Any medical condition present that in the opinion of the investigator will affect patients' clinical status.
Administration of a radioisotope within 10 physical half lives prior to study enrollment
Pregnancy and lactation

Arm && Interventions

Group	Intervention	Description
Intraoperative dual-modality imaging	Indium-111-DOTA-Girentuximab-IRDye800CW	Patients receive a single intravenous dose of Indium-111-DOTA-Girentuximab-IRDye800CW. At day 4 or 5 after antibody injection a whole body planar scan and SPECT/CT scan will be acquired. At day 7 standard of care (partial) nephrectomy will be performed. This will be extended with the use of dual-modality imaging.
Intraoperative dual-modality imaging	SPECT/CT	Patients receive a single intravenous dose of Indium-111-DOTA-Girentuximab-IRDye800CW. At day 4 or 5 after antibody injection a whole body planar scan and SPECT/CT scan will be acquired. At day 7 standard of care (partial) nephrectomy will be performed. This will be extended with the use of dual-modality imaging.
Intraoperative dual-modality imaging	Intraoperative dual-modality imaging	Patients receive a single intravenous dose of Indium-111-DOTA-Girentuximab-IRDye800CW. At day 4 or 5 after antibody injection a whole body planar scan and SPECT/CT scan will be acquired. At day 7 standard of care (partial) nephrectomy will be performed. This will be extended with the use of dual-modality imaging.

Primary Outcome Measures

Name	Time	Method
Fluorescent signal at time of surgery	During surgery	Can the tumor be identified by the fluorescent signal? Yes/No. Can the tumor be distinguished from normal tissue? Yes/No

Secondary Outcome Measures

Name	Time	Method
Optimal dose of the dual-labeled antibody preparation	4 weeks	Tumor to background ratio will be evaluated for each dose.
Safety of dual-labeled antibody injection as assessed by the number of participants with grade 3 or 4 Adverse Events according to CTCAE v4.0	4 weeks	The number of participants with grade 3 or 4 Adverse Events according to CTCAE v4.0 will be scored.
Blood levels of the dual-labeled antibody	60, 120 and 180 minutes after injection and 4 and 7 days after injection	Blood samples will be measured for radioactivity in a gamma counter at different timepoints after injection. This will be expressed as percentage injected dose per gram (%ID/g).