title: (124)I-huA33 antibody PET of colorectal cancer.
abstract: Humanized A33 (huA33) is a promising monoclonal antibody that recognizes A33 antigen, which is present in more than 95% of colorectal cancers and in normal bowel. In this study, we took advantage of quantitative PET to evaluate (124)I huA33 targeting, biodistribution, and safety in patients with colorectal cancer. We also determined the biodistribution of (124)I-huA33 when a large dose of human intravenous IgG (IVIG) was administered to manipulate the Fc receptor or when (124)I-huA33 was given via hepatic arterial infusion (HAI).
  
  
  METHODS
  We studied 25 patients with primary or metastatic colorectal cancer; 19 patients had surgical exploration or resection. Patients received a median of 343 MBq (44.4-396 MBq) and 10 mg of (124)I-huA33. Nineteen patients received the antibody intravenously and 6 patients via HAI, and 5 patients also received IVIG.
  
  
  RESULTS
  Ten of 12 primary tumors were visualized in 11 patients. The median concentration in primary colon tumors was 0.016% injected dose per gram, compared with 0.004% in normal colon. The PET-based median ratio of hepatic tumor uptake to normal-liver uptake was 3.9 (range, 1.8-22.2). Quantitation using PET, compared with well counting of serum and tissue, showed little difference. Prominent uptake in bowel hindered tumor identification in some patients. Pharmacokinetics showed that patients receiving IVIG had a significantly shorter serum half-time (41.6 ± 14.0 h) than those without (65.2 ± 9.8 h). There were no differences in clearance rates among the intravenous group, IVIG group, and HAI group, nor was there any difference in serum area under the curve, maximum serum concentration, or volume of distribution. Weak titers of human-antihuman antibodies were observed in 6 of 25 patients. No acute side effects or significant toxicities were associated with huA33.
  
  
  CONCLUSIONS
  Good localization of (124)I-huA33 in colorectal cancer with no significant toxicity has been observed. PET-derived (124)I concentrations agreed well with those obtained by well counting of surgically resected tissue and blood, confirming the quantitative accuracy of (124)I-huA33 PET. The HAI route had no advantage over the intravenous route. No clinically significant changes in blood clearance were induced by IVIG.
authors.affiliation: Nuclear Medicine Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. carrasj1@mskcc.org
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Carrasquillo
authors.forename: Neeta
authors.initials: N
authors.lastname: Pandit-Taskar
authors.forename: Joseph A
authors.initials: JA
authors.lastname: O'Donoghue
authors.forename: John L
authors.initials: JL
authors.lastname: Humm
authors.forename: Pat
authors.initials: P
authors.lastname: Zanzonico
authors.forename: Peter M
authors.initials: PM
authors.lastname: Smith-Jones
authors.forename: Chaitanya R
authors.initials: CR
authors.lastname: Divgi
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Pryma
authors.forename: Shutian
authors.initials: S
authors.lastname: Ruan
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Kemeny
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
authors.forename: Douglas
authors.initials: D
authors.lastname: Wong
authors.forename: Jaspreet S
authors.initials: JS
authors.lastname: Jaggi
authors.forename: David A
authors.initials: DA
authors.lastname: Scheinberg
authors.forename: Mithat
authors.initials: M
authors.lastname: Gonen
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Panageas
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
mesh_terms: D000368:Aged; D019540:Area Under Curve; D003106:Colon / Q000000981:diagnostic imaging; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology* / Q000628:therapy; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000378:metabolism / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography / Q000379:methods*; D011446:Prospective Studies; D016499:Radioimmunotherapy / Q000379:methods; D016896:Treatment Outcome
chemical_list: C104258:GPA33 protein, human; D016756:Immunoglobulins, Intravenous; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins