Nuclear Medicine and Biology
Volume 36, Issue 1 , Pages 39-45, January 2009

Synthesis and biodistribution of lipophilic and monocationic gallium radiopharmaceuticals derived from N,N′-bis(3-aminopropyl)-N,N′-dimethylethylenediamine: potential agents for PET myocardial imaging with 68Ga

  • Yui-May Hsiao

      Affiliations

    • Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907, USA
    • ,
  • Carla J. Mathias

      Affiliations

    • Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907, USA
    • ,
  • Shiaw-Pyng Wey

      Affiliations

    • Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907, USA
    • ,
  • Phillip E. Fanwick

      Affiliations

    • Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA
    • ,
  • Mark A. Green

      Affiliations

    • Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 765 494 1445; fax: +1 765 496 3367.

Received 9 May 2008; received in revised form 18 September 2008; accepted 21 October 2008.

Abstract 

Introduction

In locations that lack nearby cyclotron facilities for radionuclide production, generator-based 68Ga radiopharmaceuticals might have clinical utility for positron emission tomography (PET) studies of myocardial perfusion and other physiological processes.

Methods

The lipophilic and monocationic 67Ga-labeled gallium chelates of five novel hexadentate bis(salicylaldimine) ligands the bis(salicylaldimine), bis(3-methoxysalicylaldimine), bis(4-methoxysalicylaldimine), bis(6-meth,oxysalicylaldimine), and bis(4,6-dimethoxysalicylaldimine) of N,N′-bis(3-aminopropyl)-N,N′-dimethylethylenediamine (BAPDMEN), were prepared. The structure of the unlabeled [Ga(4-MeOsal)2BAPDMEN]+PF6− salt was determined by X-ray crystallography, and the biodistribution of each of the 67Ga-labeled gallium chelates was determined in rats following intravenous administration and compared with the biodistribution of [86Rb]rubidium chloride.

Results

The [Ga(4-MeOsal)2BAPDMEN]+PF6− complex exhibited the expected pseudo-octahedral N4O22− coordination sphere about the Ga3+ center with a trans disposition of the phenolate oxygen atoms. All five 67Ga radiopharmaceuticals were found to afford the desired myocardial retention of the radiogallium. The [67/68Ga][Ga(3-MeOsal)2BAPDMEN]1+ radiopharmaceutical appears to have the best properties for myocardial imaging, exhibiting 2% of the injected dose in the heart 1 min and 2 h postinjection and very high heart/nontarget ratios (heart/blood ratios of 7.6±1.0 and 54±10 at 1 and 120 min, respectively; heart/liver ratios of 1.8±0.4 and 39±3 at 1 and 120 min, respectively).

Conclusions

Most of these new agents, particularly [67/68Ga][Ga(3-MeOsal)2BAPDMEN]1+, would appear superior to previously reported bis(salicylaldimine) ligands of N,N′-bis(3-aminopropyl)ethylenediamine as candidates for PET imaging of the heart with 68Ga.

Keywords: Gallium-68, Positron emission tomography, PET, Radiopharmaceuticals, Myocardial imaging

To access this article, please choose from the options below

Login to an existing account or Register a new account.

  • Purchase this article for 31.50 USD (You must login/register to purchase this article)

    Online access for 24 hours. The PDF version can be downloaded as your permanent record.

  • Subscribe to this title

    Get unlimited online access to this article and all other articles in this title 24/7 for one year.

  • Claim access now

    For current subscribers with Society Membership or Account Number.

  • Visit SciVerse ScienceDirect to see if you have access via your institution.
 

PII: S0969-8051(08)00232-1

doi:10.1016/j.nucmedbio.2008.10.010

Nuclear Medicine and Biology
Volume 36, Issue 1 , Pages 39-45, January 2009

Article Tools

* Image Usage & Resolution