Dentin matrix proteins and soluble factors: intrinsic regulatory signals for healing and resorption of dental and periodontal tissues?

PURPOSE: Targeted radionuclide therapy (TRT), specifically peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE is an established treatment for somatostatin receptor-expressing neuroendocrine tumors across different grades; however, its efficacy in other tumors expressing somatostatin receptors remains less defined. This study aimed to evaluate the safety and efficacy of PRRT with [177Lu]Lu-DOTA-TATE in patients with medullary thyroid cancer (MTC) who presented with progressive recurrence or metastases refractory to standard therapies.

METHODS

Ten patients with MTC (3 females, 7 males; mean age 45.0 ± 13.0 years) underwent slow intravenous injection of [177Lu]Lu-DOTA-TATE combined with lysine-arginine co-infusion in 2000 mL normal saline. Each patient received a median of 4 cycles (IQR: 3.0-5.3) with a mean activity of 5.5 ± 1.5 GBq per cycle. Post-treatment imaging and serial measurements of calcitonin and carcinoembryonic antigen (CEA) were performed. Hematologic and biochemical toxicities were assessed according to CTCAE criteria.

RESULTS

Calcitonin levels showed a marked numerical decline from 6452.6 ± 8565.7(median:1897.5, interquartile range:127-12993.8) pg/mL to 540.9 ± 632.1 (390, IQR;141.8-723.3) pg/mL, although this change did not reach conventional statistical significance (P = 0.093), while CEA levels decreased significantly from 119.0 ± 186.2 (40, IQR:10.9-199) ng/ml ng/mL to 56.1 ± 67.9 (22, deIQR:5.7-112.3) ng/mL (P = 0.017). Based on calcitonin levels, biochemical response, stable disease, and progression were observed in 4, 4, and 2 patients, respectively; in contrast, CEA showed a biochemical response in 3 patients, with the remaining 7 demonstrating stable disease and no cases of biochemical progression. The median percentage reductions from baseline were clinically meaningful, reaching - 39.3% for calcitonin and - 25.8% for CEA. On imaging assessment, the best overall response comprised partial response in 4 patients, stable disease in 4 patients, and progressive disease in 2 patients. Only grade 1 hematologic toxicity was observed, with no hepatic or renal toxicity detected. White blood cell counts declined from 6144.4 ± 2362.3/µL to 4927.8 ± 1635.3/µL (P = 0.027), while other hematologic, renal, and hepatic parameters remained stable.

CONCLUSION

[177Lu]Lu -DOTA-TATE PRRT was safe and effective in controlling disease progression and reducing tumor markers in MTC patients unresponsive to conventional therapy, supporting further evaluation in larger studies.