RT Journal Article SR Electronic T1 Immuno-PET Using Anticarcinoembryonic Antigen Bispecific Antibody and 68Ga-Labeled Peptide in Metastatic Medullary Thyroid Carcinoma: Clinical Optimization of the Pretargeting Parameters in a First-in-Human Trial JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1505 OP 1511 DO 10.2967/jnumed.116.172221 VO 57 IS 10 A1 Caroline Bodet-Milin A1 Alain Faivre-Chauvet A1 Thomas Carlier A1 Aurore Rauscher A1 Mickael Bourgeois A1 Evelyne Cerato A1 Vincent Rohmer A1 Olivier Couturier A1 Delphine Drui A1 David M. Goldenberg A1 Robert M. Sharkey A1 Jacques Barbet A1 Francoise Kraeber-Bodere YR 2016 UL http://jnm.snmjournals.org/content/57/10/1505.abstract AB Earlier clinical studies reported a high sensitivity of pretargeted immunoscintigraphy using murine or chimeric anticarcinoembryonic antigen (CEA) bispecific antibody (BsMAb) and peptides labeled with 111In or 131I in medullary thyroid carcinoma (MTC). Preclinical studies showed that new-generation humanized recombinant anti-CEA × antihistamine-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 68Ga-labeled IMP288 for immuno-PET in relapsed MTC patients with calcitonin serum levels greater than 150 pg/mL. Methods: Five cohorts (C1–C5) of 3 patients received variable molar doses of TF2 and approximately 150 MBq of 68Ga-IMP288 after different pretargeting time intervals (C1: 120 nmol TF2, 6 nmol IMP288, 24 h; C2: 120 nmol TF2, 6 nmol IMP288, 30 h; C3: 120 nmol TF2, 6 nmol IMP288, 42 h; C4: 120 nmol TF2, 3 nmol IMP288, 30 h; and C5: 60 nmol TF2, 3 nmol IMP288, 30 h). TF2 and 68Ga-IMP288 pharmacokinetics were monitored. Whole-body PET was recorded 60 and 120 min after 68Ga-IMP288 injection. Tumor maximal SUV (T-SUVmax) and T-SUVmax–to–mediastinum blood-pool (MBP) SUVmean ratios (T/MBP) were determined. Results: 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. 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-to-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. Pharmacokinetics 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. Conclusion: High tumor uptake and contrast can be obtained with pretargeted anti-CEA immuno-PET in relapsed MTC patients, especially using optimized pretargeting parameters: a BsMAb-to-peptide mole ratio of 20 and 30 h pretargeting delay.