Twins in spirit part IV – [¹⁷⁷Lu] 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 [⁶⁸Ga]DOTA-3-iodo-Tyr3-octreotate ([⁶⁸Ga]HA-DOTATATE), a DOTATATE derivative with an increased binding affinity to hsst5, the current retrospective analysis is exploring the therapeutic potential of [177Lu]HA-DOTATATE. Methods: Eighteen patients with metastatic NET (G1/G2) were treated using [177Lu]DOTATATE and/or [177Lu]HA-DOTATATE, and dosimetric results of both tracers were compared. Results: Using [177Lu]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 [¹⁷⁷Lu]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 [¹⁷⁷Lu]HA-DOTATATE vs. [¹⁷⁷Lu]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 [¹⁷⁷Lu]DOTATATE (2.4 ± 5.6) compared to [¹⁷⁷Lu]HA-DOTATATE (1.5 ± 3.6). Conclusion: Both tracers showed marked inter-pa-tient variation in their dosimetry, and no significant differences in dosimetry of [¹⁷⁷Lu]HA-DOTATATE and [¹⁷⁷Lu]DOTATATE were observed when taking all patients into account. Thus, [¹⁷⁷Lu]HA-DOTATATE appears viable for PRRT, although it was marginally inferior regarding kidney dose and tumour-to-kidney dose ratio compared to the established [¹⁷⁷Lu]DOTATATE.