Introduction
Molecular radiotherapy (MRT) using 177Lu-DOTATATE is increasingly utilized in the treatment regime of primary refractory or poorly responding patients.
A phase 2 trial is in progress to evaluate the efficacy and safety of this treatment in neuroblastoma. It incorporates patient-specific whole body, tumour and normal organ dosimetry. Avoidance of unacceptable bone marrow and renal toxicities is essential for safety, and knowledge of tumour dose is desirable for correlation with response.
We present here a methodology for molecular radiotherapy dosimetry for this formal phase 2 clinical trial, in which accurate whole-body, tumour and organ-sensitive doses are a key component for improving the therapeutic index and minimisation of toxicity. This methodology involves accurate determination of time-activity curves derived from the correlation of probe counting methods with planar and SPECT/CT imaging.
Methods
Children with relapsed or refractory high-risk neuroblastoma are assessed for suitability for in-patient peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE by 68Ga-DOTATATE PET/CT. The administered activity of the first fraction of 177Lu DOTATATE is weight-based (75MBq/Kg). Activity for subsequent administrations at 8 to 12 week intervals – 4 fractions in total - depends on the whole-body radiation dose received and the haematological toxicity from previous administrations. Whole-body dose is determined by ceiling-mounted scintillation probe monitoring, performed regularly by carers over 4 days; and gamma camera imaging at 6 time points with whole body and SPECT/CT imaging for critical organ and tumour dose distribution/dosimetry.
Results
To date, 26 fractions of therapy have been administered to 16 patients in total. A complete set of probe and imaging data has been successfully acquired for every fraction delivered.
Mean whole-body dose for each patient, from fraction 1 (75MBq/kg) was 0.28Gy (range 0.19 – 0.39), which allowed dose escalation to 100MBq/kg for fraction 2.
Conclusions
Use of accurate dosimetry enables effective monitoring of organ sensitivity and enables safe dose-escalation for 177Lu-DOTATATE in Neuroblastoma.