Producción Científica Profesorado

Radiopharmacokinetic and dosimetric parameters of 188Re-lanreotide in athymic mice with induced human cancer tumors



Molina Trinidad, Eva María

2006

Eva M. Molina-Trinidad, Consuelo Arteaga de Murphy, Guillermina Ferro- Flores, Eduardo Murphy-Stack, Helgi Jung-Cook. Radiopharmacokinetic and Dosimetric Parameters of 188Re-lanreotide in athymic mice with induced Human Cancer Tumor. International Journal of Pharmaceutics. 310 (2006) 125-130. DOI: http://dx.doi.org/10.1016/j.ijpharm.2005.11.043


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-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 111In, and 90Y. A direct labeling method was used to label lanreotide with 188Re. Athymic mice with implanted human cancer tumors (uterine-cervix, renal, and neuroblastoma) were injected with radiochemically pure 188Re-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 (1.524 h post-injection) confirming 188Re-lanreotide remains bound to the tumor. The estimated tumor absorbed dose was 460 mGy/MBq. Human effective dose was 0.0182 mSv/MBq. Therefore, 188Re-lanreotide is a good candidate for PRMRT and a clinical trial is being planned in order to acquire individual dosimetric data.



Producto de Investigación




Artículos relacionados

Educación al Paciente Diabético

Tacrolimus Levels in Adult Patients With Renal Transplant

Therapeutic 188Re-lanreotide: determination of radiopharmacokinetic parameters in rats

Therapeutic Drug Monitoring of Vancomycin

Radiopharmacokinetic and dosimetric parameters of 188Re-lanreotide in athymic mice with induced huma...

Gold nanoparticles conjugated to benzoylmercaptoacetyltriglycine and L-cysteine methylester