124I-huA33 antibody PET of colorectal cancer

Nuclear Medicine Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Journal of Nuclear Medicine (Impact Factor: 5.56). 08/2011; 52(8):1173-80. DOI: 10.2967/jnumed.110.086165
Source: PubMed

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).
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.
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.
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.

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Available from: Achim A Jungbluth, Aug 13, 2015
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    • "Fluorescence-based, laparoscopic imaging , using antibodies targeting antigens found on tumour cells, has already shown considerable potential (Mahmood, 2010; Tiernan et al, 2012). In non-invasive imaging, iodine-124 labelled antibodies to CEA have been administered to enhance PET cancer scanning (Schoffelen et al, 2010; Boerman and Oyen, 2011; Carrasquillo et al, 2011; Meller et al, 2011; O'Donoghue et al, 2011; Schoffelen et al, 2012), and CEA antibodies have been conjugated to iron oxide nanoparticles to improve MRI imaging (Vigour et al, 2010). In therapeutic applications, radioisotope antibodies, usually directed towards CEA or TAG-72, have been used to deliver tumour selective radiotherapy (Meredith et al, 1996; Meyer et al, 2009; de Jong et al, 2011) and have been shown to be particularly effective in small-volume disease (Koppe et al, 2005; Barbet et al, 2012). "
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  • Journal of Nuclear Medicine 08/2011; 52(8):1171-2. DOI:10.2967/jnumed.111.089771 · 5.56 Impact Factor
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    ABSTRACT: The primary aim of this analysis was to examine the quantitative features of antibody-antigen interactions in tumors and normal tissue after parenteral administration of antitumor antibodies to human patients. Humanized anti-A33 antibody (10 mg) labeled with the positron-emitting radionuclide (124)I ((124)I-huA33) was injected intravenously in 15 patients with colorectal cancer. Clinical PET/CT was performed approximately 1 wk later, followed by a detailed assay of surgically removed tissue specimens including radioactivity counting, autoradiography, immunohistochemistry, and antigen density determination. PET/CT showed high levels of antibody targeting in tumors and normal bowel. In tissue specimens, the spatial distribution of (124)I-huA33 conformed to that of A33 antigen, and there was a linear relationship between the amount of bound antibody and antigen concentration. Antibody uptake was high in 1- to 2-mm regions of antigen-positive tumor cells (mean, ~0.05 percentage injected dose per gram) and in antigen-positive normal colonic mucosa (mean, ~0.03 percentage injected dose per gram). The estimated binding site occupancy for tumor and normal colon was 20%-50%. The in vivo biodistribution of (124)I-huA33 in human patients 1 wk after antibody administration was determined by A33 antigen expression. Our data imply that the optimal strategy for A33-based radioimmunotherapy of colon cancer will consist of a multistep treatment using a radionuclide with short-range (α- or β-particle) emissions.
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