The Bad Berka dose protocol: comparative results of dosimetry in peptide receptor radionuclide therapy using (177)Lu-DOTATATE, (177)Lu-DOTANOC, and (177)Lu-DOTATOC.

PURPOSE: The objective of this study is to analyze the in vivo behavior of the (177)Lu-labeled peptides DOTATATE, DOTANOC, and DOTATOC used for peptide receptor radionuclide therapy (PRRNT) of neuroendocrine tumors (NETs), by measuring organ and tumor kinetics and by performing dosimetric calculations. METHODS: Two hundred fifty-three patients (group 1) with metastasized NET who underwent PRRNT were examined. Out of these, 185 patients received (177)Lu-DOTATATE, 9 were treated with (177)Lu-DOTANOC, and 59 with (177)Lu-DOTATOC. Additionally, 25 patients receiving, in consecutive PRRNT cycles, DOTATATE followed by DOTATOC (group 2) and 3 patients receiving DOTATATE and DOTANOC (group 3) were analyzed. Dosimetric calculations (according to MIRD scheme) were performed using OLINDA software. RESULTS: In group 1, DOTATOC exhibited the lowest and DOTANOC the highest uptake and therefore mean absorbed dose in normal organs (whole body, kidney, and spleen). In group 2, there was a significant difference between DOTATATE and DOTATOC concerning kinetics and normal organ doses. (177)Lu-DOTATOC had the lowest uptake/dose delivered to normal organs and highest tumor-to-kidney ratio. There were no significant differences between the three peptides concerning tumor kinetics and mean absorbed tumor dose. CONCLUSIONS: The study demonstrates a correlation between high affinity of DOTANOC in vitro and high uptake in normal organs/whole body in vivo, resulting in a higher whole-body dose. DOTATOC exhibited the lowest uptake and dose delivered to normal tissues and the best tumor-to-kidney ratio. Due to large interpatient variability, individual dosimetry should be performed for each therapy cycle.

Comparison of sequential planar 177Lu-DOTA-TATE dosimetry scans with 68Ga-DOTA-TATE PET/CT images in patients with metastasized neuroendocrine tumours undergoing peptide receptor radionuclide therapy.

PURPOSE: The aim of the study was to compare sequential (177)Lu-DOTA-TATE planar scans ((177)Lu-DOTA-TATE) in patients with metastasized neuroendocrine tumours (NET) acquired during peptide receptor radionuclide therapy (PRRT) for dosimetry purposes with the pre-therapeutic (68)Ga-DOTA-TATE positron emission tomography (PET)/CT ((68)Ga-DOTA-TATE) maximum intensity projection (MIP) images obtained in the same patients concerning the sensitivity of the different methods. METHODS: A total of 44 patients (59 ± 11 years old) with biopsy-proven NET underwent (68)Ga-DOTA-TATE and (177)Lu-DOTA-TATE imaging within 7.9 ± 7.5 days between the two examinations. (177)Lu-DOTA-TATE planar images were acquired at 0.5, 2, 24, 48 and 72 h post-injection; lesions were given a score from 0 to 4 depending on the uptake of the radiopharmaceutical (0 being lowest and 4 highest). The number of tumour lesions which were identified on (177)Lu-DOTA-TATE scans (in relation to the acquisition time after injection of the therapeutic dose as well as with regard to the body region) was compared to those detected on (68)Ga-DOTA-TATE studies obtained before PRRT. RESULTS: A total of 318 lesions were detected; 280 (88%) lesions were concordant. Among the discordant lesions, 29 were (68)Ga-DOTA-TATE positive and (177)Lu-DOTA-TATE negative, whereas 9 were (68)Ga-DOTA-TATE negative and (177)Lu-DOTA-TATE positive. The sensitivity, positive predictive value and accuracy for (177)Lu-DOTA-TATE as compared to (68)Ga-DOTA-TATE were 91, 97 and 88%, respectively. Significantly more lesions were seen on the delayed (72 h) (177)Lu-DOTA-TATE images (91%) as compared to the immediate (30 min) images (68%). The highest concordance was observed for bone metastases (97%) and the lowest for head/neck lesions (75%). Concordant lesions (n = 77; mean size 3.8 cm) were significantly larger than discordant lesions (n = 38; mean size 1.6 cm) (p < 0.05). No such significance was found for differences in maximum standardized uptake value (SUV(max)). However, concordant liver lesions with a score from 1 to 3 in the 72-h (177)Lu-DOTA-TATE scan had a lower SUV(max) (n = 23; mean 10.9) than those metastases with a score of 4 (n = 97; mean SUV(max) 18) (p < 0.05). CONCLUSION: Although (177)Lu-DOTA-TATE planar dosimetry scans exhibited a very good sensitivity for the detection of metastases, they failed to pick up 9% of lesions seen on the (68)Ga-DOTA-TATE PET/CT. Three-dimensional dosimetry using single photon emission computed tomography/CT could be applied to investigate this issue further. Delayed (72 h) images are most suitable for drawing regions of interest for dosimetric calculations.

Results of individual patient dosimetry in peptide receptor radionuclide therapy with 177Lu DOTA-TATE and 177Lu DOTA-NOC.

UNLABELLED: One of the few treatment options for inoperable neuroendocrine tumors (NET) is peptide receptor radiotherapy with somatostatin analogs. In this study, we compared the dosimetric parameter uptake, half-life (kinetics), and mean absorbed organ and tumor doses of (177)Lu DOTA-NOC and (177)Lu DOTA-TATE. METHODS: Ninety-five (95) post-therapeutic dosimetric assessments using (177)Lu DOTA-TATE and 8 using (177)Lu DOTA-NOC in 69 patients with neuroendocrine tumors with high somatostatin receptor expression (verified by Ga-68 DOTA-NOC positron emission tomography/computed tomography) were analyzed. Dosimetric calculations were performed according to the Medical Internal Radiation Dose scheme. RESULTS: (177)Lu DOTA-NOC showed a significantly (p < or = 0.05; sign test) higher uptake for whole-body and normal tissue, as compared to (177)Lu DOTA-TATE, leading to a significant higher whole-body dose of 0.07 mGy/ MBq for DOTA-NOC, as compared to 0.05 mGy/MBq for DOTA-TATE. Renal and spleen uptake and radiation doses were not significantly higher for DOTA-NOC. The uptake in tumor lesions and the mean absorbed tumor dose were higher for DOTA-TATE. The red marrow dose was approximately 0.2 Gy. CONCLUSIONS: Our first results demonstrated that the higher in vitro affinity of DOTA-NOC leads to a higher uptake in normal tissues and, therefore, to an increase in the whole-body dose. The high interpatient variability of these results makes an individual patient dosimetry obligatory.