title: ¹⁷⁷Lu-Labeled Agents for Neuroendocrine Tumor Therapy and Bone Pain Palliation in Uruguay.
abstract: Lutetium-177 is an emerging radionuclide due its convenient chemical and nuclear properties. In this paper we describe the development and evaluation in Uruguay of the targeted 177Lu labelled radiopharmaceuticals EDTMP (for bone pain palliation) and DOTA-TATE (neuroendocrine tumors). We optimized the preparation of these 177Lu radiopharmaceuticals including radiolabelling, quality control methods, in vitro and in vivo stability and their therapeutic application in patients. Radiation dosimetry aspects of 177Lu are also included. Nine male patients with prostate cancer and four female patients with breast carcinoma with multiple bone metastatic lesions were treated with 177Lu-EDTMP. Four patients with gastroentheropancreatic neuroendocrine tumors (GEP-NET) and one patient with bronchial NET were treated with 1- 3 cycles with a cumulative dose of 4.44-22.2 GBq of 177Lu-DOTA-TATE. Scintigraphic images of the patients treated with 177Lu-EDTMP evidenced high and rapid uptake in bone metastasis, remaining after 7 days post administration. Images allow skeletal visualization with high definition and demonstrate increased uptake in bone metastases. For 177Lu-DOTA-TATE, partial remissions were obtained in 4 patients and the remaining patient did not show significant progression 3 months after the second cycle. No serious adverse effects were registered, even in two patients with confirmed renal disease and high risk for renal disease Dosimetry assessments confirm the predictive value of the personalized therapy with radiolabelled peptides. We found it is possible to accumulate high therapeutic doses in tumours in sequential administrations of 177Lu-DOTA-TATE, increasing the probability of biological response without significant impairment of the renal function in patients with risk factors. These results demonstrate the attractive therapeutic properties of these two 177Lu labelled agents and the feasibility of this metabolic therapy in regions far away from 177Lu producing countries.
authors.affiliation: Radiopharmacy Department, Nuclear Research Center CIN, Faculty of Sciences, Uruguay.. henia.balter@cudim.org.
authors.forename: Henia
authors.initials: H
authors.lastname: Balter
authors.forename: Trindade
authors.initials: T
authors.lastname: Victoria
authors.forename: Terán
authors.initials: T
authors.lastname: Mariella
authors.forename: Gaudiano
authors.initials: G
authors.lastname: Javier
authors.forename: Ferrando
authors.initials: F
authors.lastname: Rodolfo
authors.forename: Paolino
authors.initials: P
authors.lastname: Andrea
authors.forename: Rodriguez
authors.initials: R
authors.lastname: Graciela
authors.forename: Hermida
authors.initials: H
authors.lastname: Juan
authors.forename: De Marco
authors.initials: de M
authors.lastname: Eugenia
authors.forename: Oliver
authors.initials: O
authors.lastname: Patricia
mesh_terms: D000368:Aged; D000818:Animals; D001859:Bone Neoplasms / Q000532:radiotherapy / Q000556:secondary; D001943:Breast Neoplasms / Q000473:pathology; D004355:Drug Stability; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000473:pathology / Q000532:radiotherapy; D015282:Octreotide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009942:Organometallic Compounds / Q000008:administration & dosage*; D009943:Organophosphorus Compounds / Q000008:administration & dosage*; D010146:Pain / Q000209:etiology / Q000532:radiotherapy; D011471:Prostatic Neoplasms / Q000473:pathology; D011786:Quality Control; D011868:Radioisotopes / Q000008:administration & dosage*; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D014583:Uruguay
chemical_list: D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C119503:lutetium ethylenediaminetetramethylene phosphonic acid; C447941:lutetium Lu 177 dotatate; D015282:Octreotide