Clinical Issues Related to Fluid Management during 177Lu-Peptide Receptor Radionuclide Therapy in Metastatic Neuroendocrine Tumors with Carcinoid Heart Disease

We are discussing different clinical issues related to fluid management during the 177Lu‐DOTATATE peptide receptor radionuclide therapy (PRRT) in a patient with metastatic neuroendocrine tumors (NET) and carcinoid heart disease. Carcinoid heart disease is an uncommon complication in patients with NET. The incidence of carcinoid tumors is approximately 1 in 75,000 of the population[1] of whom up to 50% develop carcinoid syndrome and it has been noted that once the carcinoid syndrome has developed, approximately 50% of those patients will later develop carcinoid heart disease. Pathogenesis of this syndrome is due to paraneoplastic effects of vasoactive amines released from the tumor, and it manifests commonly as right heart failure due to the involvement of the tricuspid and the pulmonary valves with valvular regurgitation pattern being more common than stenosis.[2] Involvement of left‐sided valves can occur though it is less common and seen in patients with patent foramen ovale, high tumor burden, and pulmonary metastasis. The definite management in such patients includes surgical resection/debulking of the primary tumor, symptomatic relief with somatostatin analogs,[3] and surgical approaches for valvular pathology if it is significant. NETs express somatostatin receptor type 2 (SSTR2), which can be targeted using radiopeptides. 90Y‐[DOTA] 0‐tyr3‐octreotide (90Y‐DOTATOC) and/or 177Lu‐DOTATATE are used for metastatic or inoperable NETs which express SSTR2. One of the limitations of using radiopeptides is that because of their small size; they get filtered through glomerular capillaries in kidney, subsequently reabsorbed and retained in the proximal tubular cells which results in significant radiation absorbed dose to renal tissue.[4] This radiotoxicity is reduced by co‐infusion of positively charged amino acids (e g., L‐lysine and/or L‐arginine) which act by competitively inhibiting the proximal tubular reabsorption of the radiopeptide, hence decrease renal absorbed dose by 9% to 53% as shown by studies.[5] In addition, further reduction in radiation dose can be achieved by further prolonging the amino acid infusion over longer time beyond radionuclide infusion.[4] Apart from amino acid infusion, Gelofusine (a commonly used plasma expander) can be used to further reduce kidney absorbed radiation dose (by about 45%). It acts by blocking the megalin and cubilin receptor‐mediated transporter system in proximal tubules.[6] All these methods available to decrease renal absorbed dose are frequently used during PRRT procedure, but all of these require caution in managing patients who have concomitant carcinoid heart involvement. As inadvertent fluid overload can precipitate heart failure in these patients. The first issue is with the use of Gelofusine, which is a colloid used as a plasma expander. It needs caution to prevent fluid overload as experimental studies have shown that after receiving 1 l of Gelofusine over 1 h, 79% of this volume stays in the intravascular compartment and results in up to 15% rise in intravascular volume.[7] Hence, there is a possibility that it can precipitate heart failure symptoms. Furthermore, one of the side effects is a risk of anaphylaxis with use of gelofuscine.