Potentially fatal crisis after ¹⁷⁷Lu-DOTATATE therapy for paraganglioma: a case report with review of literature

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Pheochromocytoma/paraganglioma (PPGL) is a rare neuroendocrine tumor with metastatic potential. Peptide receptor radionuclide therapy with ¹⁷⁷Lu-DOTATATE, a radiolabeled somatostatin analog, has been used for the treatment of somatostatin receptor-positive PPGLs and has shown promising efficacy and generally mild toxicity. However, rare instances of fatal crises following treatment have been reported. A 50-year-old man with pheochromocytoma was admitted for ¹⁷⁷Lu-DOTATATE therapy. At the age of 49, he received ¹³¹I-MIBG therapy for the recurrence of pheochromocytoma with bone metastasis. He rejected additional radionuclide treatment because of work commitments. However, the patient’s plasma normetanephrine levels increased to >7,200 pg/mL, which worsened his pain from bone metastasis. Therefore, the patient resumed radionuclide treatment. Because his markedly elevated catecholamine levels might have induced a hypertensive crisis, ¹⁷⁷Lu-DOTATATE therapy was applied to reduce staff radiation exposure in an emergency. He developed a fever and tachycardia approximately 30 hours after ¹⁷⁷Lu-DOTATATE administration followed by cardiopulmonary arrest with hemoptysis approximately 35 hours after the administration. He was not revived. Postmortem imaging suggested alveolar hemorrhage. ¹⁷⁷Lu-DOTATATE administration might induce a fatal crisis, alveolar hemorrhage, and subsequent death. This is the first detailed report of a patient with PPGL who died shortly after ¹⁷⁷Lu-DOTATATE therapy. A review of five reported cases of fatal crises after ¹⁷⁷Lu-DOTATATE treatment suggests that high catecholamine levels are associated with a risk of crisis. In conclusion, while ¹⁷⁷Lu-DOTATATE therapy is generally considered safe, our findings underscore the potential risks of fatal crisis after therapy. Careful monitoring of patients with PPGL should be performed after treatment.