Radiopharmacokinetic and dosimetric parameters of 188Re-lanreotide in athymic mice with induced human cancer tumors.
Radiolabeled peptides, like the somatostatin analogs, have been used for peptide receptor-mediated radionuclide therapy (PRMRT) in metastatic neuroendocrine tumors. The eight amino acid peptide 3-(2-naphthalenyl)-D-alanyl-L-cysteinyl-L-tyrosyl-D-tryptophyl-L-lysyl-L-valyl-L-cysteinyl-L-threoninamide,cyclic(2-->7)-disulfide (9Cl) (lanreotide) was found to bind to the five somatostatin tumor receptors. Lanreotide has been labeled via the bifunctional chelating agent, DOTA, to (111)In, and (90)Y. A direct labeling method was used to label lanreotide with (188)Re. Athymic mice with implanted human cancer tumors (uterine-cervix, renal, and neuroblastoma) were injected with radiochemically pure (188)Re-lanreotide (1.11 MBq). The percent injected activity (%IA/g) from serial blood samples was the input data for the WinNonlin computer program to obtain radiopharmacokinetic parameters. The organs' percent injected activity per gram of tissue (%IA/g) was extrapolated to the weights of a 70 kg male model organs and the number of nuclear transitions (N) were the input for the OLINDA/EXM program to obtain dosimetry estimates. Induced uterine-cervix tumors (HeLa cells) show a mean 2.4 %IA/g uptake up to 24 h and the tumor/blood ratio was over 1.85 (1.5-24 h post-injection) confirming (188)Re-lanreotide remains bound to the tumor. The estimated tumor absorbed dose was 460 mGy/MBq. Human effective dose was 0.0182 mSv/MBq. Therefore, (188)Re-lanreotide is a good candidate for PRMRT and a clinical trial is being planned in order to acquire individual dosimetric data.
Molina-Trinidad
Eva M
EM
Departamento de Tecnología, Biofarmacia, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Av. Quetzalcóatl S/N, Estado de México 54740, México.
de Murphy
Consuelo Arteaga
CA
Ferro-Flores
Guillermina
G
Murphy-Stack
Eduardo
E
Jung-Cook
Helgi
H
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007275:Injections, Intravenous; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023421:Models, Animal; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011829:Radiation Dosage; D011868:Radioisotopes; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D012211:Rhenium; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C060347:lanreotide; D013004:Somatostatin; D012211:Rhenium