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: 6.16). 08/2011; 52(8):1173-80. DOI: 10.2967/jnumed.110.086165
Source: PubMed


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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    • "To obtain shorter blood residence times than those required for 74As-bavituximab imaging, we used the F(ab’)2 fragment of PGN635 instead of the intact antibody. Iodine-124 (124I) was chosen to label the antibody fragment since its radioactive half-life (t1/2 = 4.2 days) has been shown to be compatible with immuno-PET and it has been increasingly studied in clinic [23,24]. Moreover, 124I allows direct labeling of the antibody fragment by electrophilic radioiodination whereas other PET isotopes commonly used for immuno-PET such as copper-64 (64Cu) and zirconium-89 (89Zr) require chelator/linker molecules [25]. "
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    • "However, imaging at 48 h was generally not feasible with the activities (approximately 148 MBq) and emission times (typically 6 to 8 min per bed position) used in this study. This contrasts to the case where 124I is used to label antibodies with prolonged biological retention, for which clinically useful images may be acquired at times of up to 1 week post-administration [35,36]. This deficiency may be alleviated to some extent by the use of 3D reconstruction methods as long as appropriate corrections are included for cascade coincidences. "
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