Table 5.
Overview of clinical studies in targeted alpha therapy. QoL = quality of life, PR = partial response, SD = stable disease, PD = progressive disease, TEAE = treatment emerging adverse event, CE-US = contrast enhanced ultrasound, CE-CT = contrast enhanced CT. * n = 14 total, n = 3 213Bi.
| Author | Indication | Radiopharmaceutical | N | Aim | Findings |
|---|---|---|---|---|---|
| Ballal [90] | GEP-NETs | [225Ac]Ac-DOTA-TATE | 32 | Present early results on safety, efficacy, QoL following TAT in patients stable or refractory to [177Lu]Lu-DOTATATE | Morphological response assessed in 24/34 patients, n = 15 PR, n = 9 SD. No disease progression. Therapy was well tolerated in this population. |
| Ballal [91] | GEP-NETs | [225Ac]Ac-DOTA-TATE | 91 | Evaluate long-term outcome of TAT in GEP-NET patients in mixed population of PRRT naive and pre-treated. | TAT improved OS, even in patients refractory to prior 177Lu, with transient and acceptable toxicity. |
| Delpassand [92] | GEP-NETs | [212Pb]Pb-DOTAM-TATE | 20 | Establish safety of 212Pb-DOTAM-TATE in phase 1 dose-escalation study. | TAT well tolerated, no serious TEAEs related to the study drug. ORR of 80% at 2.50 MBq/kg/cycle, showing potential benefit over approved therapies. |
| Demirci [93] | NETs | [225Ac]Ac-DOTA-TATE | 11 | Retrospective study including 11 patients with NETs of different primary sites treated with [225Ac]Ac-DOTA-TATE. | Nine patients had PET/CT follow up. No grade III/IV toxicity, 4/9 partial response, 8/9 disease control. 225Ac is safe and effective in treatment of patients refractory to β-PRRT. |
| Giesel [94] | Hepatic NET mets | [213Bi]Bi-DOTA-TOC | 14 * | Investigate the role of contrast enhanced ultrasound in monitoring tumour response to α/β PRRT. | CE-US comparable to CE-CT and suitable for monitoring PRRT response. Decrease in perfusion indicative of tumour response. |
| Kratochwil [95] | NETs | [213Bi]Bi-DOTA-TOC | 8 | Report first in-human experience in PRRT pre-treated patients with [213Bi]Bi-DOTA-TOC. | Specific tumour uptake shown on imaging. TAT produced enduring response with moderate nephrotoxicity, is effective against β-refractory disease. |
| Kratochwil [96] | NETs | [225Ac]Ac-DOTA-TOC | 39 | Estimate optimal single cycle and cumulative activity for [225Ac]Ac-DOTA-TOC. | ~20 MBq/cycle (4-month interval) and cumulative activity ≤ 60–80 MBq avoided acute and chronic grade III/IV haemato-toxicity, some chronic renal toxicity. |
| Yadav [97] | Metastatic paraganglioma | [225Ac]Ac-DOTA-TATE | 9 | Evaluate the efficacy and safety of TAT in advanced stage paragangliomas. | 50% PR, 37.5% SD, 12.5% PD, with symptoms decreased. No grade III/IV renal or haematological toxicity. Benefit even in patients refractory to β-PRRT. |
| Zhang [98] | NETs | [225Ac]Ac-DOTA-TOC | 10 | Discuss experience with first-in-human use of novel radiopharmaceuticals, including [225Ac]Ac-DOTA-TOC, at Bad Berka. | α-PRRT was well tolerated and effective, including in one patient treated intra-arterially. |