Clinical study’s results of the safety of the radiopharmaceutical labeled with 188Re during intraarterial radioembolization

About 10% of all malignant liver neoplasms are inoperable both in Russia and worldwide. The most effective treatment of these patients is chemo- and radioembolization. For the treatment of inoperable primary and secondary liver cancer using intra-arterial radioembolization, a Russian radiopharmaceutical (RF) has been developed based on albumin microspheres with a diameter of 20-40 microns, labeled with the radioisotope rhenium-188 (RP “Gepatoren-MRRC”). Preclinical studies and phase 1 clinical studies were conducted. The aim of this work was the investigation of the safety of RP “Hepatoren-MRRC” during radioembolization in patients with inoperable primary and secondary liver cancer and selection of safe and maximum tolerated dose of the radiopharmaceutical. Intra-arterial radioembolization with Hepatoren-MRRC, 3-6 GBq, was given to 20 patients with the following diagnoses: primary liver cancer (C22.0, C22.1), metastatic liver cancer (C19.0, C22.1, C18.7, C18.0, C20.0). All patients underwent whole-body scintigraphy and SPECT at 2, 24, 48, and 72 h after procedure. Radiometry of patients' urine, which was taken within 48 h after radioembolization, was also performed. The patients were followed up for 3 months. Urinary excretion of RP was an average 23% [12%-40%] during 48 h after treatment. No accumulation of free 188Re in the thyroid gland was observed. A small (5.5%-13.2%) pulmonary shunt was observed in all patients. The diagnostic SPECT/CT image with RP «99mTc-MAA» in all patients coincided with the post-therapy SPECT/CT image with RP “Hepatoren-MRRC”. Internal radiation doses delivered to tumor ranged from 9.2 to 68.5 Gy. The values of individual radiation doses delivered to critical organs were many times less than the generally accepted dose limits for radiotherapy. Grade 1 of haematological toxicity was observed in 15 (75%) patients, grade 2 - in 3 (15%) patients, grade 3 - in 2 (10%) patients. Grade 2 of hepatological toxicity was observed in all patients. Good tolerability of RP was observed in 10 (50%) patients, satisfactory tolerability - in 7 (35%) patients and unsatisfactory tolerability - in 3 (15%) patients. No significant complications were identified during the follow-up period. One patient died 2 months after radioembolization by reason of progression of the main disease. According to the results of the Phase 1 of clinical trial we can conclude about safety and tolerability of RP “Hepatoren-MRRC” of 3-6 GBq for radioembolization in patients with inoperable liver cancer.