Toxicity and efficacy of combined radioimmunotherapy and bevacizumab in a mouse model of medullary thyroid carcinoma

Abstract

2,3‐Diaryl substituted maleimides as model compounds of conjugated maleimide polymers [poly(RMI‐alt‐Ar) and poly(RMI‐co‐Ar)] were synthesized from 2,3‐dibromo‐N‐substituted maleimide (DBrRMI) [R= cyclohexyl (DBrCHMI) and n‐hexyl (DBrHMI)] and aryl boronic acid using palladium catalysts. To clarify structures of conjugated polymer containing maleimide units at the main chain, 13C NMR spectra of 2‐aryl or 2,3‐diaryl substituted maleimides were compared with those of N‐substituted maleimide polymers. Copolymers obtained with DBrRMI via Suzuki‐Miyaura cross‐coupling polymerizations or Yamamoto coupling polymerizations were dehalogenated structures at the terminal end. This dehalogenation may contribute to the low polymerizability of DBrRMIs. On the other hand, the π‐conjugated compounds showed high solubility in common organic solvents. The N‐substituents of maleimide cannot significantly affect the photoluminescence spectra of 2,3‐diaryl substituted maleimides derivatives. The fluorescence spectra of poly(RMI‐alt‐Ar) and poly(RMI‐co‐Ar) varied with N‐substituents of the maleimide ring. When exposed to ultraviolet light of wavelength 352 nm, a series of 1,4‐phenylene‐ and/or 2,5‐thienylene‐based copolymers containing N‐substituted maleimide derivatives fluoresced in a yellow to blue color. It was found that photoluminescence emissions and electronic state of π‐conjugated maleimide derivatives were controlled by aryl‐ and N‐substituents, and maleimide sequences of copolymers. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011

Phase II Trial of Anticarcinoembryonic Antigen Pretargeted Radioimmunotherapy in Progressive Metastatic Medullary Thyroid Carcinoma: Biomarker Response and Survival Improvement

“…In preclinical studies in an MTC animal model, a synergistic effect was demonstrated using the association of RAIT with paclitaxel and improvement of tumor response using a combination of RAIT with antiangiogenic agents such as thalidomide (35,36). Thus, multimodality therapy could be a step further in the development of pRAIT.…”

Intraperitoneal Administration of Bevacizumab Intraoperatively Does Not Affect Abdominal Wound Healing in Rats

“…Furthermore, intraperitoneal administration of bevacizumab has recently been reported to induce positive therapeutic effects in experimental tumor models in mice, e.g. subcutaneous tuberous sclerosis-related tumors [34], glioblastomas [35], medullary thyroid carcinomas [36] and gastric cancers [37]. Finally, the effectiveness of bevacizumab in a rat model has been reflected by decreased intraperitoneal adhesion following a single intraoperative dose of 2.5 mg/kg of body weight i.p.…”

Emerging Trends for Radioimmunotherapy in Solid Tumors

“…[59][60][61][62] Similar enhancement in the efficacy of anti-CEA directed RIT in combination with antiangiogenic therapy was observed in medullary thyroid carcinoma. 63,64 Pretreatment with bevacizumab (anti-VEGF antibody) before RIT with an 131 I-labeled F(ab¢) 2 fragment of anti-CEA MAb F6 significantly prolonged the tumor volume doubling time from 87 -25 days to 127 -5 days without any significant change in toxicity. 63 A subsequent, more elaborate study from the same group further demonstrated the benefits of thalidomide and COBO11 (a VEGF inhibitor) in improving the efficacy of CEA-directed RIT in both small and large tumors.…”

“…63,64 Pretreatment with bevacizumab (anti-VEGF antibody) before RIT with an 131 I-labeled F(ab¢) 2 fragment of anti-CEA MAb F6 significantly prolonged the tumor volume doubling time from 87 -25 days to 127 -5 days without any significant change in toxicity. 63 A subsequent, more elaborate study from the same group further demonstrated the benefits of thalidomide and COBO11 (a VEGF inhibitor) in improving the efficacy of CEA-directed RIT in both small and large tumors. 64 Enhancement in the efficacy of RIT was only observed when the antiangiogenic agents were administered before RIT, while post-RIT antiangiogenic therapy offered no benefit.…”