Combined PRRT with 225Ac/177Lu-DOTATATE appears feasible and potentially beneficial option in advanced meningiomas. However, given the small sample size, treatment heterogeneity, and lack of controlled comparison, the findings should be interpreted with caution. Larger prospective studies are warranted.

These findings support a front-loaded 177Lu-DOTATATE strategy to maximise tumour irradiation while maintaining exposure to risk organs within safety limits. Accordingly, the LuDO-N protocol has been amended to increase administered activity to 400 MBq/kg in the first fraction for subsequent patients. Together, this work contributes to the ongoing optimisation of dosimetry-guided and intensified treatment strategies for SSTR-targeted molecular radiotherapy for high-risk neuroblastoma.

P1, N=29, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Dec 2026 | Trial primary completion date: Jun 2026 --> Dec 2026

SSTR expression in NEPC is heterogeneous. SSTR imaging can support phenotyping and selection for SSTR directed therapy in selected patients, including PSMA low disease, but prospective validation with standardized reporting is needed.

DOTATOC PET showed no uptake in the pancreatic lesion but revealed high uptake in the primary ASPS in scapula and previously unrecognized metastases in the breast and skull, indicating high somatostatin receptor (SSTR) expression. To our knowledge, this is the first report of DOTATOC uptake in ASPS, which raises the prospect of SSTR-targeted treatment with 177Lu-DOTATATE.

Hybrid PET/MRI improves hepatic lesion characterization and reduces radiation in appropriate patients, while CT/MRI remains indispensable for morphology and complications. Integrating multi-tracer PET with anatomic imaging refines risk stratification, PRRT selection, and longitudinal response assessment.

P2, N=10, Recruiting, OHSU Knight Cancer Institute | Not yet recruiting --> Recruiting | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2026 --> Dec 2027

The 213Bi daughter mostly remained with DOTATATE in tumors, decaying at the same location as 221Fr. The favorable tumor-to-normal tissue absorbed dose ratio of [225Ac]Ac-DOTATATE supports its use in patients with SSTR-expressing GEP-NETs.

P2, N=146, Recruiting, Institut du Cancer de Montpellier - Val d'Aurelle | Trial completion date: Oct 2031 --> Oct 2033 | Trial primary completion date: Oct 2031 --> Oct 2033

Tandem RLT was associated with low rates of severe late toxicity, even after very prolonged follow-up and repeated treatment courses, although gradual long-term decline in renal function was common. These data provide a rare long-term real-world benchmark for late toxicity of high-energy β-emitter-based RLT and support the long-term feasibility of tandem RLT in selected patients with NETs.

Using sunitinib as an internal control, our results show clinically significant antitumour efficacy of [177Lu]Lu-dota-tate in pretreated, progressive, somatostatin receptor-positive, metastatic pancreatic neuroendocrine tumours, and a better quality of life during the treatment phase. Late adverse events were reported in the [177Lu]Lu-dota-tate group that might affect the tolerance of subsequent lines of treatment.

Our study provides systematic preclinical evidence of sex-dependent pharmacokinetic differences in 177Lu-DOTATATE, with females demonstrating significantly higher systemic exposure than males at specific dose levels. These findings establish the systematic preclinical evidence base for sex-dependent pharmacokinetic differences in 177Lu-DOTATATE, providing a scientific rationale for incorporating sex as a stratification variable in future dosimetry-guided clinical studies.