Twins in spirit part IV - [ 177 Lu] high affinity DOTATATE. A promising new tracer for peptide receptor radiotherapy?

AIM: Besides the use of somatostatin analogues, small molecules like sunitinib and everolimus as well as conventional chemotherapy, peptide receptor radiotherapy (PRRT) using radiolabelled somatostatin analogues has gained an important role in the treatment of inoperable, metastasized neuroendocrine tumours (NET). There are various radiotracers in use. Based on our experience with the PET tracer [68 Ga]DOTA-3-iodo-Tyr3 -octreotate ([68 Ga]HA-DOTATATE), a DOTATATE derivative with an increased binding affinity to hsst5, the current retrospective analysis is exploring the therapeutic potential of [177 Lu]HA-DOTATATE.

METHODS: Eighteen patients with metastatic NET (G1/G2) were treated using [177 Lu]DOTATATE and/or [177 Lu]HA-DOTATATE, and dosimetric results of both tracers were compared.

RESULTS: Using [177 Lu]HA-DOTATATE, a mean tumour dose of 5.34 Gy/GBq (median 2.53 Gy/GBq; range 0.89-33.3 Gy/GBq) was achieved, while [177 Lu]DOTATATE delivered a tumour dose of 5.53 Gy/GBq (median 2.70 Gy/GBq; range 0.44-15.3 Gy/GBq). Organ doses for [177 Lu]HA-DOTATATE vs. [177 Lu]DOTATATE were as follows: kidney 2.31 ± 0.85 vs. 2.03 ± 0.96 Gy/GBq, liver 1.06 ± 0.79 vs. 1.67 ± 1.73 Gy/GBq, spleen 3.89 ± 4.04 vs. 4.50 ± 3.69 Gy/GBq and whole body 0.16 ± 0.10 Gy/GBq vs. 0.15 ± 0.08 Gy/GBq. Tumour-to-kidney dose ratio was slightly higher for [177 Lu]DOTATATE (2.4 ± 5.6) compared to [177 Lu]HA-DOTATATE (1.5 ± 3.6).

CONCLUSION: Both tracers showed marked inter-patient variation in their dosimetry, and no significant differences in dosimetry of [177 Lu]HA-DOTATATE and [177 Lu]DOTATATE were observed when taking all patients into account. Thus, [177 Lu]HA-DOTATATE appears viable for PRRT, although it was marginally inferior regarding kidney dose and tumour-to-kidney dose ratio compared to the established [177 Lu]DOTATATE.