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

Abstract

177 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 177 Lu. In large bulky NETs, 90 Yttrium ( 90 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 177 Lu and 90 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 90 Y-DOTATATE with 177 Lu-DOTATATE PRRT as sequential duo-PRRT in metastatic NET with (≥5 cm) including the post 90 Y-DOTATATE-PRRT imaging and also to determine early toxicity of the duo-PRRT approach. A total of 9 patients received combination of 177 Lu-DOTATATE with 90 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 90 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 90 Y-DOTATATE and 177 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 177 Lu-DOTATATE in 5 patients (55.6%), progressive disease after 177 Lu-DOTATATE in 2 patients (22.2%), and with neoadjuvant intent in 2 patients (22.2%). The total cumulative dose of 177 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 90 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 90 Y-DOTATATE (total dose of 6.2 GBq). Out of 9 patients, 8 patients showed excellent tracer concentration in lesions on post-PRRT 90 Y-DOTATATE imaging and the remaining 1 patient showed fairly adequate 90 Y-DOTATATE tracer uptake in lesion on visual anal...

New Insights in PRRT: Lessons From 2021

“…An increase in creatinine values after PRRT occurred in 12.7% of patients (grade 1–2) ( 26 ). In a small study evaluating the combination of 177 Lu-DOTATATE and 90 Y-DOTATOC therapy in 9 patients affected by NETs with a large bulky lesion (≥5 cm), posttreatment imaging showed excellent uptake of the radionuclides in the lesions in almost all patients, and only mild-grade adverse events were observed ( 31 ).…”

Combination Therapies with PRRT

“…survival and can help to determine which patients are likely to benefit from combination therapy, such as PRRT and chemotherapy [17,18]. [19,20]. CTX = chemotherapy: damaging and inhibiting DNA repair, cell proliferation arrest, tumor cell reoxygenation, and synchronization of the cell cycle or apoptosis [21].…”

“…PARPi = poly (ADP-ribose) polymerase-1 inhibitors: increases DNA double-strand breaks; blocks DNA single-strand repair [31]. [19,20]. CTX = chemotherapy: damaging and inhibiting DNA repair, cell proliferation arrest, tumor cell reoxygenation, and synchronization of the cell cycle or apoptosis [21].…”

“…On the other, Lutetium-177 alone may fail to induce a complete remission in large tumors. Therefore, PRRT combined with Lutetium-177 and Yttrium-90 might be a solution in such cases [19,20].…”

“…Anti-tumor effects of combination partners of PRRT. Dual-PRRT = dual-radionuclide peptide receptor therapy: a combination of different energy and penetration range levels to better target metastatic lesions with different sizes and nonhomogeneous somatostatin receptor (SSTR) distributions[19,20]. CTX = chemotherapy: damaging and inhibiting DNA repair, cell proliferation arrest, tumor cell reoxygenation, and synchronization of the cell cycle or apoptosis[21].…”