Abstract A013: 225Actinium and tandem 177Lutetium/225Actinium - FAPi therapy in medullary thyroid carcinoma
Bibliographic record
Abstract
Abstract Background Medullary thyroid carcinoma (MTC) has limited systemic options in advanced stages. Cancer-associated fibroblasts in tumor stroma in MTC overexpress fibroblast activation protein (FAP). FAP-targeted radioligand therapy (FAPI RLT) thus offers a novel theranostic approach. Alfa particle emitters like 225Actinium (225Ac) deliver high linear energy transfer (LET) to small, aggressive lesions, potentially improving tumor kill, where as bulkier lesions merit use of beta emitter 177lutetium alone or in tandem with 225Actinium. Methods A retrospective analysis of 31 patients with advanced/metastatic MTC treated FAPI RLT at our center was done. These patients had progressive disease despite exhausting TKI options. Pre therapy 68Ga-FAPI PET/CT demonstrated intense uptake in the lesions. 225Ac-FAPi (DOTAGA.Glu.(FAPi)_2) was administered intravenously (3.5–7.0 MBq (95–190 μCi) per treatment cycle) every 8 to 12 weeks. Patients with bulky disease received tandem therapy (two cycles of 177Lu-FAPi dimer ∼5–6 GBq of 177Lu-FAPi each followed by one cycle of 225Ac-FAPi dimer, with each cycle ∼8 weeks apart). Full blood count, renal, and liver function were obtained prior to each cycle.Treatment response was assessed biochemically (serum calcitonin and CEA) and by 68Gallium FAPI-PET/CT every 2 cycles. Progression-free survival (PFS) and overall survival (OS) were calculated from first FAPI therapy, with a follow-up duration up to 3 years. Adverse events were graded by CTCAE v5.0. Results Among 14(∼45%) MTC patients receiving tandem 177Lu/225Ac-FAPi dimer therapy, 68% patients had ∼ 52 to 67% decline in serum calcitonin and CEA levels while 17(∼55%) patients who received only 225Ac-FAPi dimer therapy demonstrated 46 to 61 % reduction in serum calcitonin and CEA levels. Restaging 68Ga-FAPi PET/CT in showed partial metabolic responses in 62.5% of patients and stable disease in 20% patients. A median PFS of ∼32 months and median OS of ∼37 months was observed. A substantial percentage of treated patients remained progression-free at 3 years post-therapy, though subsequent PFS data are awaited. Treatment was generally well tolerated with grade III hematologic toxicity observed in few patients in tandem therapy group (anemia in ∼4%, thrombocytopenia in ∼6.5%). Overall, side effects were transient and reversible. The safety profile of 225Ac-FAPI and tandem therapy mostly includes CTCAE v5.0 grade 1–2 effects. Conclusion Our study suggests FAPI RLT as an promising salvage option for advanced MTC. A substantial tumor response rate (by biochemical and PET criteria) and median PFS on the order of 2 to 3 years were observed. The safety profile appears favorable, with few low grade toxicities, mainly hematological. We conclude that tandem 177Lu/225Ac-FAPI or 225Ac-FAPI therapy can achieve encouraging disease control in carefully selected FAP-positive MTC patients, with durable PFS and OS benefits and acceptable toxicity. Citation Format: Dr Nitin Gupta. 225Actinium and tandem 177Lutetium/225Actinium - FAPi therapy in medullary thyroid carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr A013.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".