Meta-iodobenzylguanidine derivatives containing a second guanidine moiety.

  title={Meta-iodobenzylguanidine derivatives containing a second guanidine moiety.},
  author={Ganesan Vaidyanathan and Sriram Shankar and Donna J. Affleck and Kevin L. Alston and Joseph Norman and Philip C. Welsh and Holly LeGrand and Michael R Zalutsky},
  journal={Bioorganic \& medicinal chemistry},
  volume={12 7},
Radioiodinated meta-iodobenzylguanidine (MIBG) is used in the diagnosis and therapy of various neuroendocrine tumors. To investigate whether an additional guanidine function in the structure of MIBG will yield analogues that may potentially enhance tumor-to-target ratios, two derivatives-one with a guanidine moiety and another with a guanidinomethyl group at the 4-position of MIBG-were prepared. In the absence of any uptake-1 inhibiting conditions, the uptake of 4-guanidinomethyl-3-[(131)I… 
9 Citations
No-carrier-added synthesis of a 4-methyl-substituted meta-iodobenzylguanidine analogue.
  • G. Vaidyanathan, D. Affleck, M. Zalutsky
  • Chemistry, Medicine
    Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine
  • 2005
The accumulation of [131I]MeIBG by human neuroblastoma SK-N-SH cells in vitro was 87% that of [125I]MIBG, suggesting that introduction of a methyl substituent at the 4-position of MIBG did not adversely affect its biological characteristics.
A 4-methyl-substituted meta-iodobenzylguanidine analogue with prolonged retention in human neuroblastoma cells
Introduction of a methyl group at the 4-position of MIBG seems to be advantageous in terms of higher tumour retention in vitro and lower hepatic uptake in vivo, however, the slower blood clearance of MeIBG may be problematic for some applications.
Synthesis and biological effects of new hybrid compounds composed of benzylguanidines and the alkylating group of busulfan on neuroblastoma cells.
Uptake and toxicity of hybrids mBBG and pBBG in human neuroblastoma cells compared favorably to their ancestors [(131)I]-mIBG and busulfan.
A tin precursor for the synthesis of no‐carrier‐added [*I]MIBG and [211At]MABG
Radioiodinated MIBG has shown considerable promise as an imaging agent for cardiac and oncologic applications, and also as a targeted radiotherapeutic for treating patients with neuroendocrine
Design, synthesis, and biological evaluation of bifunctional thyrointegrin inhibitors: new anti-angiogenesis analogs
The synthesis of compounds incorporating long-chain moieties guanidine, urea, methyl amine and, propyl amine substitutions into the core molecular framework of tetrac were undertaken and the evaluation of the anti-angiogenic bioactivity of these compounds in the CAM model revealed no loss of activity.
Molecular Scaffolds as Double-Targeting Agents For the Diagnosis and Treatment of Neuroblastoma.
A family of novel Y-shaped scaffolds has been synthesized, which have structural analogues of MIBG covalently attached at each end of the Y-structure, yielding one specific Y- shaped structure able to be engulfed by the malignant cells, and accumulates in the tumoral tissue, at significantly higher levels than the structure containing only one single targeting agent.
A new targeting agent for the selective drug delivery of nanocarriers for treating neuroblastoma.
Novel targeting agents against neuroblastoma based on the meta-iodobenzylguanidine (MIBG) moiety were synthesized and biologically evaluated for nanocarrier vectorization, resulting in the improved cellular uptake in tumoral cells.
Heavy atom enhanced generation of singlet oxygen in novel indenofluorene-based two-photon absorbing chromophores for photodynamic therapy
Abstract A series of indenofluorene-based two-photon absorbing chromophores ( FL0 , FL-2BrN , FL-1IN , FL-2IN , and FL-2IS ) have been designed and synthesized for photodynamic therapy (PDT).
A model of modified meta-iodobenzylguanidine conjugated gold nanoparticles for neuroblastoma treatment
127I-modified mIBG was successfully synthesized and grafted covalently to the surface of carboxylated PEG-GNPs. The particles were not toxic to the normal fibroblast cells while specifically


Synthesis of ring- and side-chain-substituted m-iodobenzylguanidine analogues.
With the goal of developing MIBG analogues with improved targeting properties especially for oncologic applications, several radioiodinated ring- and side-chain-substituted MIBG analogues were
Biological evaluation of ring- and side-chain-substituted m-iodobenzylguanidine analogues.
A number of ring- and side-chain-substituted m-iodobenzylguanidine analogues were evaluated for their lipophilicity, in vitro stability, uptake by SK-N-SH human neuroblastoma cells in vitro, and
Development of a kit-form analog of metaiodobenzylguanidine.
A AIBG shows an affinity for the heart and adrenal medullae of dog and monkey similar to that of MIBG and shows improved selectivity for the adrenergic nerves of the heart as demonstrated by chemical sympathectomy studies.
Release mechanisms of [125I]meta-iodobenzylguanidine in neuroblastoma cells: evidence of a carrier-mediated efflux.
The findings suggest that stimulated [125I]MIBG release is mediated by a carrier, most probably the uptake carrier working in a reverse mode, while a minimal fraction of [ 125I] MIBG is released by an exocytotic mechanism.
No-carrier-added iodine-131-FIBG: evaluation of an MIBG analog.
Iodine-131-FIBG is an analog of MIBG with prolonged binding to neuroblastoma cells in vitro and retention in the myocardium in vivo.
Extragranular storage of the neuron blocking agent meta-iodobenzylguanidine (MIBG) in human neuroblastoma cells.
The data suggest that extravesicular retention of MIBG in SK-N-SH cells is solely due to efficient re-uptake of accumulated drug after leaking from the cells, and appears to be a powerful system for exploring various cellular and molecular aspects of catecholamine uptake.
Metaiodobenzylguanidine to map scintigraphically the adrenergic nervous system in man.
Metaiodobenzylguanidine (MIBG) localizes in adrenergic neurons; MIBG labeled with 123I then serves as an analog of norepinephrine, and concentrations of [123I]MIBG reflect sites of adrenergic neurons
Potential organ- or tumor-imaging agents. 18. Radioiodinated diamines and bisquaternaries.
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The design, synthesis and biological evaluation of a series of nitroaryl ether-based, nonpeptide mimetics based on Merck's arylether/alpha-aminoacid/guanidine framework and incorporates a novel nitro Daryl system are described.
Improved targeting of an anti-epidermal growth factor receptor variant III monoclonal antibody in tumor xenografts after labeling using N-succinimidyl 5-iodo-3-pyridinecarboxylate.
Results suggest that SIPC is a promising method for labeling this anti-EGFRvIII mAb and possibly other mAbs that internalize after binding.