RT Journal Article
SR Electronic
T1 The Humoral Immune Response to Macrocyclic Chelating Agent DOTA Depends on the Carrier Molecule
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1697
OP 1703
VO 42
IS 11
A1 Maria Elisa Perico
A1 Marco Chinol
A1 Angelo Nacca
A1 Elena Luison
A1 Giovanni Paganelli
A1 Silvana Canevari
YR 2001
UL http://jnm.snmjournals.org/content/42/11/1697.abstract
AB The chelating agent 1,4,7,10-tetraazacyclododecane-N,N′, N″,N‴-tetraacetic acid (DOTA) is used to label monoclonal antibodies (mAbs) and peptides with 90Y. DOTA allows the generation of clinically useful stable metallic radioconjugates for the treatment of a variety of tumors, but its immunogenicity has remained controversial. In this study, we evaluated the immune response to DOTA in a preclinical mouse model and in patients entered in a clinical trial. Methods: Sera were obtained from BALB/c mice injected intraperitoneally or subcutaneously with different doses and formulations of syngeneic and xenogeneic mAbs or peptide (murine mAb Mov19 [mM19]; its chimeric version; murine V/human C ChiMov19 [cM19]; or Tyr3-octreotide)-DOTA conjugates. Sera from patients with neuroendocrine tumors, enrolled in a protocol for somatostatin receptor–mediated radionuclide therapy with 90Y-DOTA-d-Phe1-Tyr3-octreotide (DOTATOC), were also collected before and after each treatment. Levels and specificity of antibody response to relevant (Mov19, ChiMov19, or Tyr3-octreotide) and nonrelevant (human serum albumin) DOTA targets were tested by enzyme-linked immunosorbent assay and competition assays. An anti-DOTA mAb (IgG1) derived from a ChiMov19-DOTA immunized mouse was used, in a competitive radioimmunoassay, to determine the efficiency of DOTA presentation on the different carriers. Results: Depending on the immunogenicity and dosage of the mAb, a specific anti-DOTA response was revealed in the preclinical system. However, DOTA–peptide conjugate induced no immune-detectable response against either chelator or carrier. DOTA was poorly presented on small peptides, as determined using the anti-DOTA mAb. Conclusion: A humoral response against DOTA is possible, but only as a consequence of the response elicited against the carrier. Octreotide was not immunogenic. Thus, 90Y-DOTATOC can be considered a safe and useful tool for receptor-mediated radionuclide therapy of somatostatin receptor–overexpressing tumors.