Endogenous and exogenous somatostatin receptors are commonly targeted for imaging using radiopharmaceutical analogues of somatostatin. Ligand binding activates receptor-mediated signaling. We assessed whether somatostatin receptor type 2A (SSTR2A) imaging can be uncoupled from signal transduction. In both human fibrosarcoma (HT1080) and human embryonic kidney (HEK293) cells, reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay found similar levels of expression of hemagglutinin A tagged SSTR2A (HA-SSTR2A) or the same fusion protein with a deletion of the C-terminus beyond amino acid 314 (HA-SSTR2Delta314). Scatchard analysis demonstrated similar degrees of ligand binding by the wild-type or mutant receptor to (111)In-octreotide in both cell pairs. Cyclic guanosine monophosphate (cGMP) production and inhibition of forskolin-induced cylic adenosine monophosphate (cAMP) production were evaluated at the signaling level, and growth inhibition was evaluated at the cellular level before and after stimulation. Unlike wild-type receptor, HA-SSTR2Delta314 was deficient in inhibiting forskolin-induced cAMP production (p < .05) and in inciting cGMP (p < .05) production; furthermore, at the cellular level, HA-SSTR2Delta314 was deficient in inhibiting cell proliferation (p < .05). Yet tumors expressing HA-SSTR2Delta314 could be imaged in vivo. Thus, in vivo imaging of SSTR2 can be uncoupled from cAMP and cGMP signaling as well as growth inhibition.