title: Phase I clinical trial of the (131)I-labeled anticarcinoembryonic antigen CIGB-M3 multivalent antibody fragment.
abstract: Center for Genetic Engineering and Biotechnology (CIGB)-M3 is a trivalent recombinant single-chain Fv antibody fragment specific for carcinoembryonic antigen (CEA). Preclinical studies with radiolabeled CIGB-M3 have showed that the antibody fragment accumulates in human colon tumor xenografts growing in nude mice. A Phase I clinical trial was carried out to determine safety, biodistribution, and pharmacokinetics of the radiolabeled CIGB-M3 in two groups of patients with CEA+ colorectal cancers. Group I (10 patients) received a single intravenous injection of 0.3 mg of (131)I-CIGB-M3 (16.7-23.3 mCi/mg). Group II (7 patients) received 1 mg (5-7 mCi/mg). No adverse events related to the injected product were recorded, and no immunology response was detected up to 6 months after the injection. Tumors were detected in 15 of the 17 studied cases. The pharmacokinetic profile showed beta half-times of 14.1 and 6.3 hours for Groups I and II, respectively. Seventy-two (72) hours after the administration of the product, 85% of the total injected activity was excreted in urine in the form of free (131)I. The kidneys were identified as the organs that can limit the maximum tolerated dose. The (131)I-CIGB-M3 was safe in patients with colorectal cancer. The biodistribution and pharmacokinetic data suggest that the product can be further tested for molecular radiotherapy of CEA+tumors.
authors.affiliation: Nuclear Medicine Department, National Institute of Oncology and Radiobiology, La Habana, Cuba.
authors.forename: Gilmara Pimentel
authors.initials: GP
authors.lastname: González
authors.forename: Idrian García
authors.initials: IG
authors.lastname: García
authors.forename: Joaquín González
authors.initials: JG
authors.lastname: González
authors.forename: Lincidio Pérez
authors.initials: LP
authors.lastname: Sánchez
authors.forename: Milagros Velasco
authors.initials: MV
authors.lastname: Mirabal
authors.forename: Carlos Calderón
authors.initials: CC
authors.lastname: Marín
authors.forename: Fausto L García
authors.initials: FL
authors.lastname: Ruiz
authors.forename: Elizeth Garcia
authors.initials: EG
authors.lastname: Iglesias
authors.forename: Rosalina López
authors.initials: RL
authors.lastname: de Queralta
authors.forename: Ramón Ropero
authors.initials: RR
authors.lastname: Toirac
authors.forename: Marta Ayala
authors.initials: MA
authors.lastname: Avila
authors.forename: Adlín López
authors.initials: AL
authors.lastname: Díaz
authors.forename: Pedro A López
authors.initials: PA
authors.lastname: Saura
authors.forename: Jorge V
authors.initials: JV
authors.lastname: Gavilondo
authors.forename: Juan P Oliva
authors.initials: JP
authors.lastname: González
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000737:chemistry*; D002272:Carcinoembryonic Antigen / Q000378:metabolism*; D005260:Female; D006801:Humans; D007128:Immunoglobulin Fragments / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000379:methods; D011874:Radiometry; D057127:Single-Chain Antibodies / Q000737:chemistry; D013997:Time Factors
chemical_list: D000906:Antibodies; D002272:Carcinoembryonic Antigen; D007128:Immunoglobulin Fragments; D007457:Iodine Radioisotopes; D057127:Single-Chain Antibodies