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Pretargeting parameters for the use of anti-carcinoembryonic antigen (CEA) bispecific monoclonal antibody TF2 and the 68 Ga-labeled IMP288 peptide for immuno-PET have been optimized in a first-in-humans study performed on medullary thyroid carcinoma (MTC) patients (the iPET-MTC study). The aim of this post hoc analysis was to determine the sensitivity of immuno-PET in relapsing MTC patients, in comparison with conventional imaging and 18 F-l-dihydroxyphenylalanine ( 18 F-DOPA) PET/CT. Methods: Twenty-five studies were analyzed in 22 patients. All patients underwent immuno-PET 1 and 2 h after 68 Ga-IMP288 injection pretargeted by TF2, in addition to neck, thoracic, abdominal, and pelvic CT; bone and liver MRI; and 18 F-DOPA PET/CT. The gold standard was histology or confirmation by one other imaging method or by imaging follow-up. Results: In total, 190 lesions were confirmed by the gold standard: 89 in lymph nodes, 14 in lungs, 46 in liver, 37 in bone, and 4 in other sites (subcutaneous tissue, heart, brain, and pancreas). The number of abnormal foci detected by immuno-PET was 210. Among these, 174 (83%) were confirmed as true-positive by the gold standard. Immuno-PET showed a higher overall sensitivity (92%) than 18 F-DOPA PET/CT (65%). Regarding metastatic sites, immuno-PET had a higher sensitivity than CT, 18 F-DOPA PET/CT, or MRI for lymph nodes (98% vs. 83% for CT and 70% for 18 F-DOPA PET/CT), liver (98% vs. 87% for CT, 65% for 18 F-DOPA PET/CT, and 89% for MRI), and bone (92% vs. 64% for 18 F-DOPA PET/CT and 86% for MRI), whereas sensitivity was lower for lung metastases (29% vs. 100% for CT and 14% for 18 F-DOPA PET/CT). Tumor SUV max at 60 min ranged from 1.2 to 59.0, with intra- and interpatient variability. Conclusion: This post hoc study demonstrates that anti-carcinoembryonic antigen immuno-PET is an effective procedure for detecting metastatic MTC lesions. Immuno-PET showed a higher overall sensitivity than 18 F-DOPA PET/CT for disclosing metastases, except for the lung, where CT remains the most effective examination., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

This prospective study evaluated the imaging performance of a novel pretargeting immunologic PET (immuno-PET) method in patients with human epidermal growth factor receptor 2 (HER2)-negative, carcinoembryonic antigen (CEA)-positive metastatic breast cancer, compared with CT, bone MRI, and 18 F-FDG PET. Methods: Twenty-three patients underwent whole-body immuno-PET after injection of 150 MBq of 68 Ga-IMP288, a histamine-succinyl-glycine peptide given after initial targeting of a trivalent anti-CEA, bispecific, antipeptide antibody. The gold standards were histology and imaging follow-up. Tumor SUVs (SUV max and SUV mean ) were measured, and tumor burden was analyzed using total tumor volume and total lesion activity. Results: The total lesion sensitivity of immuno-PET and 18 F-FDG PET were 94.7% (1,116/1,178) and 89.6% (1,056/1,178), respectively. Immuno-PET had a somewhat higher sensitivity than CT or 18 F-FDG PET in lymph nodes (92.4% vs. 69.7% and 89.4%, respectively) and liver metastases (97.3% vs. 92.1% and 94.8%, respectively), whereas sensitivity was lower for lung metastases (48.3% vs. 100% and 75.9%, respectively). Immuno-PET showed higher sensitivity than MRI or 18 F-FDG PET for bone lesions (95.8% vs. 90.7% and 89.3%, respectively). In contrast to 18 F-FDG PET, immuno-PET disclosed brain metastases. Despite equivalent tumor SUV max , SUV mean, and total tumor volume, total lesion activity was significantly higher with immuno-PET than with 18 F-FDG PET ( P = 0.009). Conclusion: Immuno-PET using anti-CEA/anti-IMP288 bispecific antibody, followed by 68 Ga-IMP288, is a potentially sensitive theranostic imaging method for HER2-negative, CEA-positive metastatic breast cancer patients and warrants further research., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Earlier clinical studies reported a high sensitivity of pretargeted immunoscintigraphy using murine or chimeric anticarcinoembryonic 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 × 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 68 Ga-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 68 Ga-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 68 Ga-IMP288 pharmacokinetics were monitored. Whole-body PET was recorded 60 and 120 min after 68 Ga-IMP288 injection. Tumor maximal SUV (T-SUV max ) and T-SUV max -to-mediastinum blood-pool (MBP) SUV mean ratios (T/MBP) were determined., Results: In C1, T-SUV max 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-SUV max and T/MBP. Further increasing the delay to 42 h in C3 decreased T-SUV max 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-SUV max 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., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Objectives: A phase I pretargeted radioimmunotherapy trial (EudractCT 200800603096) was designed in patients with metastatic lung cancer expressing carcinoembryonic antigen (CEA) to optimize bispecific antibody and labeled peptide doses, as well as the delay between their injections., Methods: Three cohorts of three patients received the anti-CEA × anti-histamine-succinyl-glycine (HSG)-humanized trivalent bispecific antibody (TF2) and the IMP288 bivalent HSG peptide. Patients underwent a pretherapeutic imaging session S1 (44 or 88 nmol/m(2) of TF2 followed by 4.4 nmol/m(2), 185 MBq, of (111)In-labeled IMP288) and, 1-2 weeks later, a therapy session S2 (240 or 480 nmol/m(2) of TF2 followed by 24 nmol/m(2), 1.1 GBq/m(2), of (177)Lu-labeled IMP288). The pretargeting delay was 24 or 48 h. The dose schedule was defined based on preclinical TF2 pharmacokinetic (PK) studies, on our previous clinical data using the previous anti-CEA-pretargeting system, and on clinical results observed in the first patients injected using the same system in Netherlands., Results: TF2 PK was represented by a two-compartment model in which the central compartment volume (Vc) was linearly dependent on the patient's surface area. PK was remarkably similar, with a clearance of 0.33 ± 0.03 L/h/m(2). (111)In- and (177)Lu-IMP288 PK was also well represented by a two-compartment model. IMP288 PK was faster (clearance 1.4-3.3 L/h). The Vc was proportional to body surface area, and IMP288 clearance depended on the molar ratio of injected IMP288 to circulating TF2 at the time of IMP288 injection. Modeling of image quantification confirmed the dependence of IMP288 kinetics on circulating TF2, but tumor activity PK was variable. Organ-absorbed doses were not significantly different in the three cohorts, but the tumor dose was significantly higher with the higher molar doses of TF2 (p < 0.002). S1 imaging predicted absorbed doses calculated in S2., Conclusion: The best dosing parameters corresponded to the shorter pretargeting delay and to the highest TF2 molar doses. S1 imaging session accurately predicted PK as well as absorbed doses of S2, thus potentially allowing for patient selection and dose optimization., Trial Registration: ClinicalTrials.gov NCT01221675 (EudractCT 200800603096).

We report herein the results we obtained and the limitations we experienced during the production and use of a bank of Epstein-Barr virus (EBV)-transformed human cytotoxic T lymphocytes (EBV-CTLs). To assess the feasibility and toxicity of this strategy, we selected and stored, in liquid nitrogen, 4 billion EBV-CTLs from each of the 13 selected donors. Subsequently, in a multicenter phase I/II study, 11 patients with EBV-associated lymphoma resistant to conventional treatments received 1-3 doses of 5 million EBV-CTLs/kg with 1-3 and 0-4 compatibilities for human leukocyte antigen (HLA)-I and HLA-II, respectively. Except for one event of fever after injection, no immediate or delayed toxicity, no graft versus host disease, and no graft rejection attributable to CTL infusion were observed. Three patients presented complete remission and 1 partial remission after treatment. Considering the clinical options currently available, and the constrains associated with CTL preparation and implementation, we conclude that CTL banks should consist of a reasonably small number of cell lines with documented specificities. This objective could be more easily achieved if the few homozygous donors for the most frequent HLA alleles of the targeted population could be made available for such a project.

The standard management for advanced-stage epithelial ovarian cancer is optimum cytoreductive surgery followed by platinum based chemotherapy. However, retroperitoneal lymph node resection remains controversial. The multiple directions of the lymph drainage pathway in ovarian cancer have been recognized. The incidence and pattern of lymph node involvement depends on the extent of the disease and the histological type. Several published cohorts suggest the survival benefit of pelvic and para-aortic lymphadenectomy. A recent large randomized trial have demonstrated the potential benefit for surgical removal of bulky lymph nodes in term of progression-free survival but failed to show any overall survival benefit because of a critical methodology. Further randomised trials are needed to balance risks and benefits of systematic lymphadenectomy in advanced-stage disease. CARACO is a French ongoing trial, built to bring a reply to this important question. A huge effort for inclusion of the patients, and involving new teams, are mandatory., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Despite the weak immunogenicity of gangliosides, a limited number of highly specific murine monoclonal antibodies (MAbs) were elicited. This study investigated the reactivity and the structure of the VH and V kappa genes of nine hybridomas obtained from independent fusions producing antibodies against disialogangliosides GD2 and GD3 and their O-acetylated derivatives. These antibodies depended on four types of V kappa genes. They were also encoded by VH genes of the J558 family (5 out of 9) and occasionally by VH genes of the S107, 7183, and 3609 families, rearranged with a variety of DH and JH genes. The 8B6 and 7H2 MAbs specific for GD2-O-acetylated, respectively, used the VH gene of the S107 and 7183 families. The length of H chain CDR3 ranged from 8 to 11 amino acids. A set of S107 and 3609 germline genes closed from A/J murine fetal liver and matched with the VH segment of hybridomas 8B6 and 10B8 revealed somatic mutations. Although the relative number of sequences does not preclude any formal conclusions regarding the preferential use of V genes in the immune recognition of carbohydrate structures, our results clearly indicate that MAbs directed to very similar structures as GD2 and GD3 were encoded by different VH and V kappa genes.

The present epidemiological study was carried out 700 national servicemen doing service at the barracks Carlo Alberto Dalla Chiesa of Fosano (Cuneo) in the period April-August 1989, for the purposes of determining the state of oral health in a large sample of the Italian young male population and the diffusion of actions aimed at caries prophylaxis. The DMF index of the group in question is 7.14. 83.44% of DMF teeth were subjected to conservative dental treatment, 5.58% were extracted and 10.98% presented ongoing processes of caries requiring treatment. The results obtained show that, although caries is still very widespread in Italy in relation to other European countries and the United States, considerable progress has been made compared to the past as regards the secondary prevention of the pathology. Nevertheless, much remains to be done for the primary prophylaxis of caries. These data were confirmed by those obtained on periodontopathies. Although, the serious forms of periodontal disease in youth are very rare, very few conscripts are aware of the most elementary principles of oral hygiene.

A case of impacted teeth and maxillary sinus cyst is reported. The etiopathogenesis, anatomo-pathology, symptomatology and diagnosis of impacted and heterotopic teeth are also described.

A case of median mandibular cyst is reported. The main aspects of the origin, diagnosis and therapy of median mandibular cysts are described, together with endodontic problems and differential diagnosis.

Clinical and statistical investigation on the use of ceftizoxime in the treatment of peri- and postoperative infections in odontostomatological and maxillofacial surgery. A sample of 48 patients in the Odontostomatologic Division of the Hospital of Asti is examined. Principles and experience of surgical antimicrobial prophylaxis according to its antibacterial activity, pharmacokinetic properties and therapeutic use are reported.