Pharmacokinetics and imaging of 212Pb-TCMC-trastuzumab after intraperitoneal administration in ovarian cancer patients.
OBJECTIVE
Study distribution, pharmacokinetics, and safety of intraperitoneal (IP) 212Pb-TCMC-trastuzumab in patients with HER-2-expressing malignancy.


METHODS
IP 212Pb-TCMC-trastuzumab was delivered, after 4 mg/kg intravenous (IV) trastuzumab, to 3 patients with HER-2-expressing cancer who had failed standard therapies. Patients were monitored for toxicity and pharmacokinetics/dosimetry parameters.


RESULTS
Imaging studies after 0.2 mCi/m2 (7.4 MBq/m2) show little redistribution out of the peritoneal cavity and no significant uptake in major organs. Peak blood level of the radiolabeled antibody, determined by decay corrected counts, was <23% injected dose at 63 hours; maximum blood radioactivity concentration was 6.3nCi/mL at 18 hours. Cumulative urinary excretion was ≤6% in 2.3 half-lives. The maximum external exposure rate immediately post-infusion at skin contact over the abdomen averaged 7.67 mR/h and dropped to 0.67 mR/h by 24 hours. The exposure rates at the other positions monitored (axilla, chest, and femur) decreased as a function of distance from the abdomen. The data points correlate closely with 212Pb physical decay (T1/2=10.6 hours). Follow-up >6 months showed no evidence of agent-related toxicity.


CONCLUSIONS
Pharmacokinetics and imaging after 0.2 mCi/m2 IP 212Pb-TCMC-trastuzumab in patients with HER-2-expressing malignancy showed minimal distribution outside the peritoneal cavity, ≤6% urinary excretion, and good tolerance.
1 Department of Radiation Oncology, University of Alabama at Birmingham , Birmingham, Alabama.
Ruby F
RF
Meredith
Julien
J
Torgue
Michael T
MT
Azure
Sui
S
Shen
Souheil
S
Saddekni
Eileen
E
Banaga
Ronda
R
Carlise
Patty
P
Bunch
Daniel
D
Yoder
Ronald
R
Alvarez
D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D015331:Cohort Studies; D005260:Female; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D006801:Humans; D007274:Injections, Intraperitoneal; D017879:Isothiocyanates / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D007856:Lead Radioisotopes / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000532:radiotherapy*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D000068878:Trastuzumab
D061067:Antibodies, Monoclonal, Humanized; D006571:Heterocyclic Compounds; D017879:Isothiocyanates; D007856:Lead Radioisotopes; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C410212:2-(4-isothiocyanatobenzyl)-1,4,7,10--tetraaza-1,4,7,10-tetra-(2-carbamoylmethyl)cyclododecane; C508053:ERBB2 protein, human