TABLE 3.

Actinium-225-peptide receptor radionuclide therapy in NET treatment.

Peptide	Tumor types	Model	Key findings	Authors	References
Pre-clinical
DOTATOC	Pancreatic NET	Xenograft	Activity up to 20 kBq had no significant toxic effect. Effective accumulation in xenografted NETs Reduced growth of NETs, and improved therapeutic efficacy	Miederer et al.	(117)
DOTATOC	Pancreatic tumor cells	In vitro	225Ac and 177Lu triggered-γH2AX-foci formation is an early key parameter in predicting response to internal radiotherapy.	Graf et al.	(156)
DOTATATE	Lung NET	Xenograft	1st Preclinical study for 225Ac-DOTATATE; Activity up to 111 kBq had no significant toxicity Significantly decreased tumor volume, increased tumor growth delay, and prolonged time to experimental endpoint for animals bearing both tumor types	Tafreshi et al.	(157)
Peptide	Tumor types	Patient number	Key findings	Authors	References
Clinical
DOTATOC	NETs	34 patients	Promising treatment efficacy in various patients Suggesting comparative trials of α and β are needed.	Kratochwil et al.	(87)
DOTATOC	NETs	10 patients	The very first intra-arterial targeted alpha peptide radionuclide therapy using 225Ac DOTATOC 225Ac DOTATOC PRRT was very well-tolerated and effective.	Zhang et al.	(158)
DOTATATE	GEP-NET	32 patients	First clinical experience on efficacy and safety 225Ac-DOTATATE TAT as a promising treatment option for patients who are refractory to 177Lu-DOTATATE therapy	Ballal et al.	(159)
DOTATATE	Gastric NET	Case report	First whole-body and SPECT/CT images demonstrating high tumor uptake of 225Ac -DOTATATE.	Ocak et al.	(160)
DOTATATE	Rectal NET	Case report	Whole-body and SPECT/CT imaging results encourage the use of 225Ac -DOTATATE as a primary modality of treatment in advanced NET with metastases.	Kamaleshwaran et al.	(161)
DOTATOC	Liver NET	Case report	225Ac-PRRT in a β-radiation-refractory NET patient was shown to be safe and effective.	Zhang et al.	(162)
DOTATOC	Thymus NET	Case report	No adverse effects observed after 225Ac-DOTATOC TAT in patients with metastatic neuroendocrine tumors failing β-PRRT.	Zhang et al.	(163)
DOTATATE	Rectal NET	Case report	Using 225Ac-DOTATATE as first-line treatment presents a novel strategy for metastatic NETs with high skeletal disease burden.	Satapathy et al.	(164)
DOTATATE	NET-CUP	Case report	First case report demonstrating thyroid dysfunction developed after 225Ac-DOTATATE therapy in a patient with NET with unknown primary.	Kavanal et al.	(165)
DOTATATE	Pancreatic NET	Case report	225Ac-DOTATATE was well-tolerated at early stage of treatment, and patient demonstrated excellent response.	Budlewski et al.	(166)
DOTATATE	NET-CUP	Case report	First case who received actinium-225 first line with almost complete response at a single dosage	Alan Selçuk et al.	(167)
DOTATATE	GEP-NET	91	225Ac-DOTATATE TAT showed improved overall survival, even in patients refractory to prior 177Lu-DOTATATE treatment with transient and acceptable adverse effects	Ballal et al.	(168)