Immuno-PET using anti-CEA bispecific antibody and 68Ga-labeled peptide in metastatic medullary thyroid carcinoma: clinical optimization of the pretargeting parameters in a First-in Human trial.

Earlier clinical studies reported a high sensitivity of pretargeted immunoscintigraphy using murine or chimeric anti-carcinoembryonic antigen (CEA) bispecific antibody (BsMAb) and peptides labeled with (111)In or (131)I in medullary thyroid carcinoma (MTC). Preclinical studies showed that new generation humanized recombinant anti-CEA x anti-histamine-succinyl-glycine (HSG) trivalent BsMAb TF2 and radiolabeled HSG peptide (IMP288) present good features for PET. This study aimed at optimizing molar doses and pretargeting interval of TF2 and (68)Ga-labeled IMP288 for immuno-PET in relapsed MTC patients with calcitonin serum levels > 150 pg/ml. Five cohorts (C1 to C5) of 3 patients received variable molar doses of TF2 and ~150 MBq (68)Ga-IMP288 after different pretargeting time intervals (C1: 120 nmol TF2, 6 nmol IMP288, 24 h; C2: 120, 6, 30 h; C3: 120, 6, 42 h; C4: 120, 3, 30 h; C5: 60, 3, 30 h). TF2 and (68)Ga-IMP288 pharmacokinetics were monitored. Whole-body PET was recorded 60 and 120 min after (68)Ga-IMP288 injection. Tumor maximal standardized uptake value (T-SUVmax) and T-SUVmax/mediastinum blood pool (MBP) SUVmean ratios (T/MBP) were determined. In C1, T-SUVmax and T/MBP ranged from 4.09 to 8.93 and 1.39 to 3.72 at 60 min and 5.14 to 11.25 and 2.73 to 5.38 at 120 min, respectively. Because of the high MBP, the delay was increased to 30 h in C2, increasing T-SUVmax and T/MBP, (15.25 to 33.33 and 6.43 to 26.24 at 60 min, respectively). Further increasing the delay to 42 h in C3 decreased T-SUVmax and T/MBP, showing that 30 h was the most favorable delay. In C4, the TF2/peptide mole ratio was increased to 40 (delay 30 h), resulting in high T-SUVmax but with higher MBP than in C2. In C5 the molar dose of TF2 was reduced, resulting in lower imaging performance. PK demonstrated a fast TF2 clearance and a clear relationship between blood activity clearance and the ratio between the molar amount of injected peptide to the molar amount of circulating TF2 at the time of peptide injection. High tumor uptake and contrast can be obtained with pretargeted anti-CEA immuno-PET in relapsed MTC patients, especially using optimized pretargeting parameters: BsMAb/peptide mole ratio of 20 and 30 h-pretargeting delay. Copyright © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Citation

Caroline Bodet-Milin, Alain Faivre-Chauvet, Thomas Carlier, Aurore Rauscher, Mickael Bourgeois, Evelyne Cerato, Vincent Rohmer, Olivier Couturier, Delphine Drui, David M Goldenberg, Robert M Sharkey, Jacques Barbet, Francoise Kraeber-Bodéré. Immuno-PET using anti-CEA bispecific antibody and 68Ga-labeled peptide in metastatic medullary thyroid carcinoma: clinical optimization of the pretargeting parameters in a First-in Human trial. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2016 May 26

PMID: 27230928

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