Initial clinical evaluation of indigenous 90 Y-DOTATATE in sequential duo-PRRT approach ( 177 Lu-DOTATATE and 90 Y-DOTATATE) in neuroendocrine tumors with large bulky disease: Observation on tolerability, 90 Y-DOTATATE post- PRRT imaging characteristics (bremsstrahlung and PETCT) and early adverse effects

• Published in: World journal of nuclear medicine Vol. 20; no. 1; p. 73
• Main Authors: Parghane, Rahul V, Mitra, Arpit, Bannore, Trupti Upadhye, Rakshit, Sutapa, Banerjee, Sharmila, Basu, Sandip
• Format: Journal Article
• Language: English
• Published: Austria 01-01-2021
• Subjects: Tandem PRRT; peptide receptor radionuclide therapy (PRRT); 177Lu-DOTATATE; duo-PRRT; 90Y-DOTATATE; 68Ga-DOTATATE PET-CT
• ISSN: 1450-1147

Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) alone has lesser potential in the clinical setting of neuroendocrine tumor (NET) with large bulky disease and nonhomogeneous somatostatin receptors (SSTR) distribution, owing to lower energy (Eβmax 0.497 MeV) and a shorter particle penetration range (maximum 2-4 mm) of
Lu. In large bulky NETs,
Yttrium (
Y) has the theoretical advantages because of a longer beta particle penetration range (a maximum soft tissue penetration of 11 mm). Therefore, a combination of
Lu and
Y is a theoretically sound concept that can result in better response in metastatic NET with large-bulky lesion and non-homogeneous SSTR distribution. The aim of the study was to determine the feasibility of combining
Y-DOTATATE with
Lu-DOTATATE PRRT as sequential duo-PRRT in metastatic NET with (≥5 cm) including the post
Y-DOTATATE-PRRT imaging and also to determine early toxicity of the duo-PRRT approach. A total of 9 patients received combination of
Lu-DOTATATE with
Y-DOTATATE (indigenously prepared and approved) through sequential duo-PRRT approach. These 9 NET patients were included and analyzed in this study. All 9 patients had undergone post-PRRT
Y-DOTATATE imaging, including a whole-body planar bremsstrahlung imaging followed by regional single-photon emission computed tomography (SPECT)-computed tomography (CT) imaging and also a regional positron emission tomography-computed tomography imaging. Grading of
Y-DOTATATE and
Lu-DOTATATE uptake was done on post-PRRT imaging by both modalities. The size of the lesions ranged from 5.5 cm to 16 cm with average size of 10 cm before sequential duo-PRRT was decided. Sequential duo-PRRT was administered because of stable, unresponsive disease following
Lu-DOTATATE in 5 patients (55.6%), progressive disease after
Lu-DOTATATE in 2 patients (22.2%), and with neoadjuvant intent in 2 patients (22.2%). The total cumulative dose of
Lu-DOTATATE before duo-pRRT ranged from 11.84 GBq to 37 GBq per patient and average administered dose of 27.21 GBq per patient in this study. Out of 9 patients, 8 patients received single cycle of
Y-DOTATATE (ranging from 2.66 GBq to 3.4 GBq per patient with average administered dose of 3.12 GBq per patient). One patient received two cycles of
Y-DOTATATE (total dose of 6.2 GBq). Out of 9 patients, 8 patients showed excellent tracer concentration in lesions on post-PRRT
Y-DOTATATE imaging and the remaining 1 patient showed fairly adequate
Y-DOTATATE tracer uptake in lesion on visual analysis. There was matched
Y-DOTATATE uptake with
Ga-DOTATATE and also with
LuDOTATATE in all 9 patients. The sequential duo-PRRT was well tolerated by all patients. Two patients (22.2%) developed mild nausea, one patient (11.1%) developed transient mild-grade hemoglobin toxicity, and one patient (11.1%) developed mild-grade gastrointestinal symptoms (loose motion and abdominal pain). No nephrotoxicity, hepatotoxicity, and other hematological toxicity was observed. The combination of the indigenous
Y-DOTATATE with
Lu-DOTATATE PRRT in NET as sequential duo-PRRT was well tolerated, feasible and safe in stable, unresponsive/progressive disease following single isotope
Lu-DOTATATE therapy and also in neoadjuvant PRRT setting with large bulky lesion (≥≥5cm). Post-PRRT
Y-DOTATATE imaging showed excellent
Y-DOTATATE uptake in nearly all NET patients. Mild-grade early adverse effects were easily manageable and controllable in this sequential duo-PRRT approach.