Radioimmunodetection of cancer of gastrointestinal tract and liver metastasis with I-131 anti-CEA and I-131 anti-CA19-9 monoclonal antibody cocktail (IMACIS-1)

Abstract

We evaluated the intravenous infusion of a cocktail of I-131 anti-CEA and anti-CA19-9 monoclonal antibody F(ab')2 (IMACIS-1) in patients with gastrointestinal neoplasm and liver metastases in order to assess its efficacy in detecting the presence of cancer. Seven patients with primary or recurrent gastrointestinal cancer in whom liver metastases were also detected were studied. Accumulation of radioactivity in the primary tumor was seen in only one patient. Visualization of the liver metastases was achieved in all patients. Thus detection of liver metastasis was better than in primary or recurrent tumors. While tumor visualization was most often seen in the 3 day image, optimal visualization of the tumor was seen at 5-7 days. There was no correlation between the serum concentration of CEA or CA19-9 and the visualization of tumors. Serum kinetics of I-131 IMACIS-1 showed biexponential components with a 1st phase T1/2 of 5.0 hours and 2nd phase T1/2 of 34.7 hours. The mean whole body (I-131) half-life determined from the whole-body scans was 1.95 days. The mean urinary excretion of I-131 in 7 days was 85%. This value agreed closely with total radioactivity retention detected by scanning. This series of studies demonstrated the potential utility of a cocktail of antibodies consisting of an anti-CEA and an anti-CA19-9 monoclonal F(ab')2.

Retooling a Blood-Based Biomarker: Phase I Assessment of the High-Affinity CA19-9 Antibody HuMab-5B1 for Immuno-PET Imaging of Pancreatic Cancer

“…A practical limitation of imaging with 89 Zr-labeled antibodies, including MVT-2163, is the relatively long timeframe required to reach high tumor uptake (6). In the present study, we observed a continued increase in tumor uptake of MVT-2163 for 7 days, whereas tumor uptake of small molecules such as 18 Ffluorodeoxyglucose typically plateaus within a few hours after injection. The slow uptake and excretion of antibodies is a significant logistic problem for the clinical use of MVT-2163 PET/CT.…”

“…The slow uptake and excretion of antibodies is a significant logistic problem for the clinical use of MVT-2163 PET/CT. It also results in an effective dose of 0.51 mSv/MBq which is in the range of effective doses reported for other 89 Zr-labeled antibodies such as the Her2 antibodies 89 Zr-Trastuzumab, 0.48 mSv/MBq and 89 Zr-Pertuzumab, 0.54 mSv/MBq, and the PSMA antibody 89 Zr-J591, 0.38 mSv/MBq (25)(26)(27), but several-fold higher than for 18 F-fluorodeoxyglucose (0.029 mSv/ MBq; ref. 28).This high radiation exposure will likely limit the use of MVT-2163 for screening and early detection of PDAC with currently available PET/CT systems.…”

“…Our clinical results confirm the excellent targeting of CA19-9-positive malignancies with MVT-2163 in preclinical studies and indicate that MVT-2163 is promising for the detection and staging of CA19-9-positive malignancies. In the past, a few radiolabeled antibodies have been evaluated to target CA19-9-positive malignancies in humans, mainly using the gamma emissions of 131 I (18,19). Due to the inherent limitations in imaging and radiation dose properties, the use of 131 I has been discontinued.…”

Use of spiral and non‐spiral computed tomography arterial portography in the detection of potentially malignant liver masses

“…There have been promising, but very early, experimental reports of using positron emission tom0graphy,2~ phosphorus-3 1 MRI s p e c t r o~c o p y~~~~~ and monoclonal antibodies. 26 In conclusion, we recommend CTAP as a valuable method for the pre-operative evaluation of patients being considered for liver mass resection and patients being considered for non-hepatic malignancy surgery when the presence of any liver metastases will affect the decision to proceed with surgery.…”

Effect of radioimmunoscintigraphy in management of recurrent colorectal cancer

“…RIS has resulted from advances in nuclear medicine and molecular biology. RIS using CEA antibodies, either solely 8±15 or in combination with antibodies raised to CA19±9 16,17 , or antibodies raised against other tumour cell antigens 18,19 , has been employed in the detection of recurrent colorectal cancer with reported high sensitivity and speci®city. There seems little point, however, in widespread adoption of these techniques in routine follow-up if current therapies are incapable of altering the prognosis for the individual in whom scanning is suggestive of recurrence.…”