Twins in spirit part IV – [¹⁷⁷Lu] high affinity DOTATATE

Summary

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 1.6 ± 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-patient 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.

Zusammenfassung

Ziel: Basierend auf unseren Erfahrungen mit dem PET-Tracer[⁶⁸Ga]DOTA-3-iodo-Tyr³ octreotate ([⁶⁸Ga]HA-DOTATATE) wurde in der vorliegenden retrospektiven Analyse das therapeutische Potential von Lu-177 markiertem HA-DOTATATE untersucht. Methode: 18 Patienten mit metastasiertem NET (G1/G2) wurden mit [¹⁷⁷Lu]DOTATATE und/oder [¹⁷⁷Lu]HA-DOTATATE therapiert und in einer retrospektiven Auswertung die dosimetri- schen Ergebnisse beider Radiopharmaka verglichen. Ergebnisse: Mit [¹⁷⁷Lu]HA-DOTATATE wurde eine mittlere Tumordosis von 5.34 Gy/ GBq (Median 2.53 Gy/GBq; Spannbreite 0.89-33.3 Gy/GBq) erreicht, während mit [¹⁷⁷Lu]DOTATATE eine mittlere Tumordosis von 5.53 Gy/GBq (Median 2.70 Gy/GBq; Spannbreite 0.44-15.3 Gy/GBq) erzielt wurde. Die folgenden Organdosen wurden für [¹⁷⁷Lu]HA-DOTATATE ermittelt: Niere 2.31 ± 0.85 Gy/GBq, Leber 1.06 ± 0.79 Gy/ GBq, Milz 3.89 ± 4.04 Gy/GBq und Ganzkörper 0.16 ± 0.10 Gy/GBq. Für [¹⁷⁷Lu]DOTATATE wurden folgende Dosen bestimmt: Niere 2.03 ± 0.96 Gy/GBq, Leber 1.67 ± 1.73 Gy/ GBq, Milz 4.50 ± 3.69 Gy/GBq und Ganzkörper 0.15 ± 0.08 Gy/GBq. Das Tumor-zu- Nierenverhältnis war für [¹⁷⁷Lu]DOTATATE (2.4 ± 5.6) etwas besser verglichen mit [¹⁷⁷Lu]HA-DOTATATE (1.5 ± 3.6). Schlussfolgerung: Die dosimetrischen Ergebnisse beider Radiotracer weisen eine hohe interindividuelle Schwankungsbreite auf. Signifikante Unterschiede hinsichtlich Organ- und Tumordosen konnten nicht festgestellt werden. Die mittlere Tumordosis und das Tumor- zu-Nierenverhältnis waren für [¹⁷⁷Lu]HA- DOTATATE tendenziell schlechter als für [¹⁷⁷Lu]DOTATATE.

Keywords

PRRT - dosimetry - HA-DOTATATE - DOTATATE

Schlüsselwörter

PRRT - Dosimetrie - HA-DOTATATE - DOTATATE

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