Radiopeptide Therapy using Lu-177 3BP-227 in a Patient with Pancreatic Adenocarcinoma

Objectives Neurotensin receptor subtype-1 (NTR1) is overexpressed in metastatic pancreatic adenocarcinoma, which has a very poor prognosis. Lu-177 labeled 3BP-227, an NTR1 antagonist, has been tested in preclinical models with promising results. We demonstrate dosimetric results in a case of pancreatic adenocarcinoma, treated with Lu-177 3BP-227.

Methods 59 year-old female patient with newly-diagnosed adenocarcinoma of the pancreatic head and lymph node metastases as well as peritoneal carcinosis with massive ascites (requiring thrice weekly asites tapping), s.p. 7 cycles of chemotherapy, received 1400 MBq Lu-177 3BP-227. Dosimetry was performed according to the MIRD scheme and using OLINDA/EXM software to estimate the dose to whole body, normal organs and metastases. Blood samples were drawn to determine the blood kinetics and to estimate the absorbed dose to red marrow.

Results Administration of Lu-177 3BP-227 was well tolerated without any significant adverse effects. Post-therapy planar and SPECT/CT images demonstrated significant uptake in the primary tumor. The whole body uptake showed a bi-exponential decline, half-lives being 5.8h and 30.5h. The kidneys followed an exponential clearance with a half-life of 50h. The primary tumor showed an exponential decline with half-life of 40h. The following mean absorbed doses were calculated: whole body: 0.1Gy, kidneys: 1.5Gy, primary: 1Gy, red marrow was 0.12Gy. Follow-up CT 8 weeks after therapy demonstrated a decrease in size of the primary tumor. There was no significant fall in the blood counts and serum creatinine or any of the other laboratory parameters.

Conclusions Radiopeptide therapy with higher activity of Lu-177 3BP-227 is feasible in adenocarcinoma of the pancreas with exhaustion of therapy options. Lu-177 3BP-227 holds great promise for treatment of this highly aggressive cancer.