Radioimmunotherapy of medullary thyroid cancer with iodine-131-labeled anti-CEA antibodies.
This study evaluates the pharmacokinetics, dosimetry, toxicity and therapeutic potential of radiolabeled NP-4 and MN-14 anti-CEA antibodies in medullary thyroid cancer (MTC).


METHODS
Eighteen patients with advanced MTC entered exploratory clinical studies with therapeutic doses of 131I-labeled NP-4 and MN-14 murine monoclonal antibodies (MAbs) reactive with carcinoembryonic antigen (CEA). Doses administered ranged from 46 mCi for 131I-MN-14 lgG to 195 mCi for 131I-MN-14 F(ab)2 in patients negative for human anti-mouse antibodies (HAMA).


RESULTS
The radioconjugate blood half-life (T1/2) for the whole lgG was 42.5+/-5.0 hr compared to 18.8+/- 4.1 hr for the bivalent fragments. Tumor doses of 17.5+/-11.0 and 11.4+/-6.3 cGy/mCi were estimated for 131I-MN-14 lgG and F(ab)2, respectively. Tumor/red marrow dose ratios exceeded 3:1 for most lesions. Red marrow doses of up to 350 cGy generally could be delivered with < grade 4 toxicity. Seven of 14 evaluable patients showed evidence of anti-tumor effects lasting up to 26 months, based on physical exam, tumor markers or computed tomography.


CONCLUSIONS
This study demonstrates that anti-CEA MAbs may be suitable for radioimmunotherapy of metastatic or recurrent MTC.
Juweid
M
M
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Newark, New Jersey, USA.
Sharkey
R M
RM
Behr
T
T
Swayne
L C
LC
Herskovic
T
T
Pereira
M
M
Rubin
A D
AD
Hanley
D
D
Dunn
R
R
Siegel
J
J
Goldenberg
D M
DM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D018276:Carcinoma, Medullary / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D015899:Tomography, Emission-Computed, Single-Photon
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes