Quantitative mapping of 4'-iododeoxyrubicin in metastatic squamous cellcarcinoma by secondary ion mass spectrometry (SIMS) microscopy.
Secondary ion mass spectrometry microscopy enables quantitative mapping of chemical elements in tissue sections. It was used for the detection of 127I contained in 4'-iododeoxyrubicin (IDX). Metastatic cutaneous squamous cell carcinoma from 7 patients participating in a phase I study (IDX dose, 80 mg/m2, 10-min i.v. infusion) were biopsied 10 min after drug administration and compared to 3 controls who did not receive any treatment (one squamous cell carcinoma and 2 gastric carcinomas). Biopsy specimens were fixed and embedded in methacrylate resin. Then, serial semithin sections (3 microns) were analyzed simultaneously with ionic and optimal microscopes in order to identify the histological structures given by the 31P distribution in which 127I in IDX was mapped. The iodine signal was undetected in controls and found mainly in the nuclei of tumor cells of the treated patients. Its concentration, measured in at least 30 nuclei of each specimen, was undetectable in 8% of the nuclei and 91% of them were within 1 and 16 ng/mg. The mean concentration of each specimen ranged from 5 to 23 ng/mg. This study demonstrates the capacity of ion microscopy to localize a cytotoxic drug (IDX) in a human biopsy specimen without the need for radioactive labeling and enables the evaluation of drug penetration in cancer cells which is critical for its activity.
Fragu
P
P
Microscopie ionique, INSERM U66, Villejuif, France.
Klijanienko
J
J
Gandia
D
D
Halpern
S
S
Armand
J P
JP
D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002467:Cell Nucleus / Q000648:ultrastructure; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D004341:Drug Evaluation; D006801:Humans; D007457:Iodine Radioisotopes; D008853:Microscopy / Q000379:methods; D008875:Middle Aged
D007457:Iodine Radioisotopes; C053044:4'-deoxy-4'-iododoxorubicin; D004317:Doxorubicin