Efficacy and toxicity of radioimmunotherapy with (90)Y-DOTA-peptide-ChL6 for PC3-tumored mice.
BACKGROUND
Radioimmunotherapy (RIT) is a new therapeutic modality capable of systemic delivery of radionuclides specifically to sites of metastatic cancer. The L6 monoclonal antibody has been shown to target prostate cancer in preclinical studies and, along with chimeric L6 (ChL6), has been used for RIT in breast cancer patients.


METHODS
Pharmacokinetics, blood counts, body weight, and antitumor activity of RIT with (90)yttrium-((90)Y)-DOTA-peptide-ChL6 (75-260 microCi) were determined in nude mice bearing human prostate cancer (PC3) xenografts.


RESULTS
RIT produced durable, dose-dependent antitumor effects with a 100% response rate using 112 microCi and 150 microCi (the maximum tolerated dose) of (90)Y-DOTA-peptide-ChL6. Myelotoxicity was reversible, dose-limiting, and dose-related. RIT was associated with improved survival (P = 0.05). All 5 mice in the 150-microCi group survived the 84-day study period vs. 1/8 (13%) for untreated, tumored control mice.


CONCLUSIONS
(90)Y-DOTA-peptide-ChL6 targets PC3 human prostate cancer xenografts in nude mice and has an antitumor effect. These results provide a basis for future RIT trials for patients with metastatic prostate cancer.
O'Donnell
R T
RT
Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California, USA. rtodonnell@ucdavis.edu
DeNardo
S J
SJ
DeNardo
G L
GL
Miers
L
L
Lamborn
K R
KR
Kukis
D L
DL
Meyers
F J
FJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001835:Body Weight; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006571:Heterocyclic Compounds / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009842:Oligopeptides / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010976:Platelet Count; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000592:standards*; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013047:Specific Pathogen-Free Organisms; D014407:Tumor Cells, Cultured; D014915:Whole-Body Counting; D015019:Yttrium / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015021:Yttrium Radioisotopes / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; C106337:ChL6 monoclonal antibody; D006571:Heterocyclic Compounds; D009842:Oligopeptides; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; C112391:yttrium-90-DOTA-peptide-chimeric L6; D015019:Yttrium