Effect of peptide dose on radiation dosimetry for peptide receptor radionuclide therapy with 177Lu-DOTATOC: A pilot study

Background: Optimal peptide concentration in treatment with Lu-177-DOTATOC/DOTATATE is a matter of debate. Most of the studies with peptide receptor radionuclide therapy mention peptide dose ranging between 100 and 250 mu g. The aim of this is to identify possible differences in radiation-absorbed doses (D/Gy) to tumor and kidney as a function of the peptide mass dose in order to identify the most suitable peptide dose for treatment. The therapeutic index (D-tumor/D-kidneys) was assessed as a key parameter for the treatment response. Materials and Methods: Five patients with metastasized Grade 1 to Grade 2 neuroendocrine tumor were analyzed in this study. Patients (n = 4) received two cycles of treatment with intravenously injected Lu-177-DOTATOC containing peptide mass doses of 200 mu g and 90 mu g, alternatively; one patient was treated with 90 mu g peptide mass in both the therapy cycles. Whole-body (head to mid-thigh) three-dimensional single-photon emission computerized tomography (3D SPECT)/CT images were acquired at 1, 4, 24, 48, and 72 h following the injection of Lu-177-DOTATOC. Attenuation correction for 3D SPECT images was performed using CT data acquired and fused with the SPECT data (SPECT/CT). Results: Overall, 28 target lesions (liver n = 17, lung n = 4, lymph nodes n = 1, and bone n = 2) were analyzed after 1st and 2nd therapy cycles. Tumor normalized absorbed doses varied by a factor of 74 between 0.35 and 26 mGy/MBq. Averaged over all patients, a higher normalized mean tumor dose (10.51 mGy/MBq) was achieved for a peptide dose of 200 mu g compared to 90 mu g (4.58 mGy/MBq). Kidneys doses varied by a factor of up to 4 between patients (0.25-1.0 mGy/MBq) (independent of dose cycle and peptide dose) and by a factor of up to 2 between dose cycles. The mean kidney dose was 13.7% higher for the 90 mu g peptide dose compared to 200 mu g. Given the higher tumor dose, the mean therapeutic index of a 200 mu g mass dose was considerably higher (16.95), compared to a 90 mu g mass dose (9.63). This coincided with the observation, that lesion volume reduction was more pronounced after an initial treatment with a 200 mu g mass dose. Biologically effective dose was only 5. 1%-19.3% higher than the absorbed dose for individual dose cycles. Conclusions: Higher peptide dose of 200 mu g appears to be more suitable than 90 mu g in terms of tumor dose, kidney dose, and therapeutic index for treatment with Lu-177-DOTATOC.