International Journal of Pharmaceutics 310 (2006) 125–130 Radiopharmacokinetic and dosimetric parameters of 188 Re-lanreotide in athymic mice with induced human cancer tumors Eva M. Molina-Trinidad a , Consuelo Arteaga de Murphy b,∗ , Guillermina Ferro-Flores c , Eduardo Murphy-Stack d , Helgi Jung-Cook e a Departamento de Tecnolog´ ıa (Biofarmacia), Facultad de Estudios Superiores Cuautitl´ an, Universidad Nacional Aut´ onoma de M´ exico, Av. Quetzalc´ oatl S/N, Estado de M´ exico 54740, M´ exico b Departamento de Medicina Nuclear, Instituto Nacional de Ciencias M´ edicas y Nutrici ´ on Salvador Zubir ´ an, Vasco de Quiroga # 15, Delegaci´ on Tlalpan, M´ exico D.F. 14000, M´ exico c Departamento de Materiales Radiactivos, Instituto Nacional de Investigaciones Nucleares, km 36.5 Carretera M´ exico-Toluca, Salazar, 52045 Estado de M´ exico, M´ exico d Departamento de Patolog´ ıa, Hospital Santelena, Quer´ etaro # 58, M´ exico D.F. 06700, M´ exico e Departamento de Farmacia, Facultad de Qu´ ımica, Universidad Nacional Aut´ onoma de M´ exico, Av. Universidad # 3000, Ciudad Universitaria, M´ exico D.F. 04510, M´ exico Received 18 July 2005; received in revised form 29 November 2005; accepted 29 November 2005 Available online 19 January 2006 Abstract 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-threonin- amide,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 460mGy/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. © 2005 Elsevier B.V. All rights reserved. Keywords: 188 Re-lanreotide; Implanted tumors in athymic mice; Pharmacokinetics; Dosimetry; OLINDA code 1. Introduction The selection of a labeled peptide with a radionuclide that maximizes the radiation dose in the tumor and minimizes the dose in the normal tissues constitutes an important radiophar- maceutical for targeted radiotherapy. Radiolabeled somatostatin ∗ Corresponding author. Tel.: +52 55 5487 0900x2402; fax: +52 55 5655 1076. E-mail address: consuelo murphy@yahoo.com.mx (C.A.d. Murphy). analog peptides have been used for peptide receptor-mediated radionuclide therapy (PRMRT) in metastatic neuroendocrine tumors. The vast majority of human tumors seem to over-express one or the other of five known distinct hSSSTR subtype somato- statin receptors and 111 In-DTPA-d-Phe 1 -octreotide, which binds to hSSTR2 and 5 with high affinity, has been considered a valu- able tool for the visualization of human endocrine tumors and their metastasis (Krenning et al., 1993; Reubi et al., 2000). Recently, other somatostatin analogs have been synthesized for receptor-expression molecular imaging and therapy. The 0378-5173/$ – see front matter © 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2005.11.043