Variables influencing tumor dosimetry in radioimmunotherapy of CEA-expressing cancers with anti-CEA and antimucin monoclonal antibodies.
In this study, we examined the factors that may influence tumor dosimetry in the radioimmunotherapy of solid, CEA-expressing cancers.


METHODS
Data from 119 tumors in 93 patients with CEA-expressing cancers were analyzed. The patients underwent radioimmunotherapy with the 131I-labeled IgG1 anti-CEA antibodies NP-4 (Ka = 10(8) M-1) or MN-14 (Ka = 10(9) M-1), its humanized form hMN-14, as well as the anticolon-specific antigen-p (CSAp) antibody, Mu-9. For dosimetry, the biodistribution, targeting kinetics and cumulated activity of tumors and organs were determined from planar and SPECT imaging.


RESULTS
An inverse logarithmic relationship between tumor size and antibody uptake was found for both anti-CEA antibodies, whereas no such relationship was found for Mu-9. The absolute tumor uptake was identified as the most important factor determining the radiation dose to the tumor (r = 0.9), with the biological half-life of the antibody in the tumor being of secondary importance (r = 0.5). No significant difference in tumor uptake was found between both anti-CEA antibodies, despite their tenfold difference in affinity. At comparable masses, colorectal and medullary thyroid cancers had significantly higher tumor uptakes (p = 0.02), as well as tumor-to-red marrow dose ratios, than other cancer types. The tumor half-lives of the anti-CEA antibodies were significantly lower in colorectal than in all other tumor types (p = 0.01).


CONCLUSIONS
In radioimmunotherapy, tumor uptake appears to be the most important dose-determining factor. Differences in antibody affinity are reflected by differences in the biological half-life, not the absolute uptake. Especially favorable conditions for anti-CEA antibodies seem to prevail in colorectal cancer patients having minimal disease, as well as in medullary thyroid cancer, where cytotoxic tumor doses might be expected. Antimucin antibodies may have a particular advantage in the treatment of patients with larger colorectal tumors.
Behr
T M
TM
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Newark, New Jersey, USA.
Sharkey
R M
RM
Juweid
M E
ME
Dunn
R M
RM
Ying
Z
Z
Zhang
C H
CH
Siegel
J A
JA
Goldenberg
D M
DM
D000230:Adenocarcinoma / Q000378:metabolism / Q000532:radiotherapy* / Q000556:secondary; D000368:Aged; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D005260:Female; D006207:Half-Life; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008345:Manganese / Q000627:therapeutic use; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism*; D009405:Neptunium / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes; D009077:Mucins; D011868:Radioisotopes; D008345:Manganese; D009405:Neptunium