RT Journal Article SR Electronic T1 Targeted Chemoradiation in Metastatic Colorectal Cancer: A Phase I Trial of 131I-huA33 with Concurrent Capecitabine JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 534 OP 539 DO 10.2967/jnumed.113.132761 VO 55 IS 4 A1 Rebecca A. Herbertson A1 Niall C. Tebbutt A1 Fook-Thean Lee A1 Sanjeev Gill A1 Bridget Chappell A1 Tina Cavicchiolo A1 Tim Saunder A1 Graeme J. O’Keefe A1 Aurora Poon A1 Sze Ting Lee A1 Roger Murphy A1 Wendie Hopkins A1 Fiona E. Scott A1 Andrew M. Scott YR 2014 UL http://jnm.snmjournals.org/content/55/4/534.abstract AB huA33 is a humanized antibody that targets the A33 antigen, which is highly expressed in intestinal epithelium and more than 95% of human colon cancers but not other normal tissues. Previous studies have shown huA33 can target and be retained in a metastatic tumor for 6 wk but eliminated from normal colonocytes within days. This phase I study used radiolabeled huA33 in combination with capecitabine to target chemoradiation to metastatic colorectal cancer. The primary objective was safety and tolerability of the combination of capecitabine and 131I-huA33. Pharmacokinetics, biodistribution, immunogenicity, and tumor response were also assessed. Methods: Eligibility included measurable metastatic colorectal cancer, adequate hematologic and biochemical function, and informed consent. An outpatient scout 131I-huA33 dose was followed by a single-therapy infusion 1 wk later, when capecitabine was commenced. Dose escalation occurred over 5 dose levels. Patients were evaluated weekly, with tumor response assessment at the end of the 12-wk trial. Tumor targeting was assessed using a γ camera and SPECT imaging. Results: Nineteen eligible patients were enrolled. The most frequently observed toxicity included myelosuppression, gastrointestinal symptoms, and asymptomatic hyperbilirubinemia. Biodistribution analysis demonstrated excellent tumor targeting of the known tumor sites, expected transient bowel uptake, but no other normal tissue uptake. 131I-huA33 demonstrated a mean terminal half-life and serum clearance suited to radioimmunotherapy (T1/2β, 100.24 ± 20.92 h, and clearance, 36.72 ± 8.01 mL/h). The mean total tumor dose was 13.8 ± 7.6 Gy (range, 5.1–26.9 Gy). One patient had a partial response, and 10 patients had stable disease. Conclusion: 131I-huA33 achieves specific targeting of radiotherapy to colorectal cancer metastases and can be safely combined with chemotherapy, providing an opportunity to deliver chemoradiation specifically to metastatic disease in colorectal cancer patients.