Poster Presentation Advances in Neuroblastoma Research Congress 2016

124I-hu3F8 radioimmuno-positron emission tomography (PET) in patients with neuroblastoma and other GD2-positive malignancies: preliminary results on biodistribution, pharmacokinetics and tumor targeting (#266)

Shakeel Modak 1 , Pat Zanzonico 2 , Todd Heaton 3 , Sean Carlin 4 , Serge Lyashchenko 4 , Jason Lewis 4 , Nai Kong Cheung 1 , Neeta Pandit-Taskar 4
  1. Pediatrics, Memorial Sloan Kettering Cancer Center, New York, United States
  2. Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, 10065
  3. Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States
  4. Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States

Objectives :  Anti-GD2 monoclonal antibodies (MoAbs) are currently an integral part of  therapy for high-risk neuroblastoma. However, biodistribution in patients has not been fully explored. We radio-iodinated the humanized anti-GD2 MoAb hu3F8 with the positron-emitting radioisotope 124I and investigated the biodistribution, pharmacokinetics and tumor targeting of 124I-hu3F8 in patients with neuroblastoma and other GD2-positive tumors in a first-in-human study. (Clinicaltrials.gov NCT02307630). We present preliminary results from this ongoing trial.

Methods : Patients received 3 mCi/m2 124I-hu3F8 intravenously followed by whole body (WB) PET imaging at 3-4 time points 2 to 96 hours post-injection (PI). Serial blood samples were drawn over the same time period. WB and blood clearance rates, lesion uptake and radiation absorbed dose for normal organs were analyzed using OLINDA software.

Results: Three patients (2 neuroblastoma and 1 osteosarcoma) thus far have received 124I -hu3F8 and completed study observations. No adverse events were noted. In the two neuroblastoma patients, there was highly accurate and specific targeting to metastatic disease with 100% concordance of lesions detected compared to MIBG scan. The patient with osteosarcoma underwent 124I-hu3F8 radioimmuno-PET followed by resection of a 7mm pulmonary metastasis. Autoradiography showed specific targeting of 124I-hu3F8 to areas of viable osteosarcoma cells correlating with immunohistochemical staining for GD2, but not to acellular calcified areas. Median bloo half life (T1/2) of 124I-hu3F8 bi-exponential with an early rapid T1/2 of 1.24±2.7h and delayed phase with T1/2 of 28±13.7h. Mean organ radiation absorbed dose (rad/mCi injected) was 2.96±1.58, 2.82±1.42, 2.14±1.4, and 2.22±1.11 for blood, kidney, liver and lung respectively. Whole body effective dose (rem/mCi) averaged 3.55±3.21.

Conclusions: Preliminary data from this ongoing study show that 124I-hu3F8 imaging is safe, pain-free, highly specific and sensitive. Quantitative Information could be obtained for  dosimetry calculations. Radio-iodinated hu3F8 has the potential to be used for radioimmunodetection and radioimmunotherapy of neuroblastoma and other GD2-positive tumors.