(177)Lu- labeled MOv18 as compared to (131)I- or (90)Y-labeled MOv18 has the better therapeutic effect in eradication of alpha folate receptor-expressing tumor xenografts.
BACKGROUND
The mouse monoclonal antibody MOv18, directed against the alpha-isoform of folate receptor (FR), was investigated to identify the optimal radioconjugate for radioimmunotherapy of minimal residual disease in ovarian cancer.


METHODS
Pharmacokinetics, biodistribution, long-term therapeutic efficacy and toxicity of MOv18, labeled with the beta-emitters (131)I, (90)Y and (177)Lu, were compared in a xenografted mouse model, composed by two cell lines, A431FR and A431MK, differing only for FR expression.


RESULTS
A shorter blood clearance and a higher tumor uptake were observed for (90)Y- and (177)Lu- compared to (131)I-MOv18, and a shorter blood pharmacokinetics was recorded in A431FR-bearing animals. At equitoxic maximum tolerable doses, the general irradiation by (131)I- and (90)Y-MOv18 gives rise to strong targeted effects on A431FR and nontargeted effects on A431MK tumors, while (177)Lu-MOv18 was able to eradicate small size tumor masses expressing the antigen of interest exerting only mild non-targeted effects.


CONCLUSIONS
(177)Lu-MOv18 at the maximal tolerated dose is the immunoradioconjugate with the best therapeutic window in experimental conditions of small tumor volume.
Zacchetti
Alberto
A
Unit of Molecular Therapies, Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy.
Coliva
Angela
A
Luison
Elena
E
Seregni
Ettore
E
Bombardieri
Emilio
E
Giussani
Augusto
A
Figini
Mariangela
M
Canevari
Silvana
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D058846:Antibodies, Monoclonal, Murine-Derived; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry; D007553:Isotope Labeling; D008187:Lutetium / Q000737:chemistry; D020714:Maximum Tolerated Dose; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D047368:Tumor Burden; D015021:Yttrium Radioisotopes / Q000737:chemistry
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D007457:Iodine Radioisotopes; C424863:MOv18 monoclonal antibody; D011868:Radioisotopes; D011956:Receptors, Cell Surface; D015021:Yttrium Radioisotopes; D008187:Lutetium