AbstractSigma receptors are expressed in high density in various types of cancer cells including brain tumours and are also involved in various diseases of central nervous system. This makes ligands that bind to these receptors, attractive molecular vectors for targeting radiation to the specific sites with the purpose of imaging and therapy of neurological disorders. We report synthesis of three derivatives of 4‐amino‐N‐benzylpiperidine namely, 4‐dithiocarbamato‐N‐benzylpiperidine, 4‐iminodiacetato‐N‐benzylpiperidine and 4‐(N‐benzylpiperidine)‐pyridin‐2‐ylmethyl‐amino)‐acetic acid and their radiolabeling with technetium‐99m. The in vivo evaluation of these radiolabeled compounds has been carried out in mice, for assessment of their binding affinity with sigma receptors. Of the three complexes, [99mTcN]‐4‐dithiocarbamato‐N‐benzylpiperidine, [99mTcN]Pip‐DTC exhibited the most promising characteristics with brain uptake of 0.6% ID/g at 5 min.p.i. that reduced to 0.3% ID/g after 2 h.p.i. Competition experiment carried out with [99mTcN]Pip‐DTC complex, using (+)‐pentazocine showed its specificity towards sigma receptors, as was found to be evident from reduction in the brain uptake of this complex. Introduction of iminodiacetate and pyridine moieties and subsequent radiolabeling did not result in complexes with significant potential of targeting and binding with sigma receptors. Copyright © 2010 John Wiley & Sons, Ltd.