Association of Somatostatin Receptor 2 Immunohistochemical Expression with [111In]-DTPA Octreotide Scintigraphy and [68Ga]-DOTATOC PET/CT in Neuroendocrine Tumors

In the absence of preoperative somatostatin receptor (sst) scans, knowledge of immunohistochemical sst2 tumor expression may help predicting the success of somatostatin analogue-based follow-up studies and treatment of neuroendocrine tumors (NET). We studied the association between sst immunostaining and tracer uptake in [In-111]-DTPA octreotide (DTPAOC) scintigraphy and [Ga-68]-DOTA-D-Phe(1)-Tyr(3)-octreotide (DOTATOC) positron emission tomography (PET)/computed tomography (CT). Retrospective analysis of 36 NET patients was carried out. In 40 tumors, immunohistochemical sst2, sst3, and sst5 expressions were analyzed using a pathological scoring, applying monoclonal (sst2) or polyclonal antibodies (sst3, sst5). In 14 lesions, [In-111]-DTPAOC uptake was assessed by a semiquantitative score. In 26 tumors, [Ga-68]-DOTATOC PET/CT was quantified using an uptake score and maximal standard uptake value (SUVmax). Combined and separate qualitative analysis of sst scans revealed significant associations between increased tracer uptake and immunohistochemical sst2 detection (combined: rho = 0.56, p = 0.0002, [In-111]-DTPAOC: rho = 0.63, p = 0.0152, and [Ga-68]-DOTATOC: rho = 0.52, p = 0.0065, respectively). In contrast, sst3 and sst5 immunostaining was not associated with tracer uptake (all p > 0.14). The semiquantitative immunohistochemical score for sst2 was associated with the [Ga-68]-DOTATOC uptake score and SUVmax values (rho = 0.67, p = 0.0002 and rho = 0.63, p = 0.0010, respectively), but not with the [In-111]-DTPAOC uptake score (rho = 0.24, p = 0.4). In patients without preoperative sst scans, knowledge of immunohistochemical sst2 expression may help estimating the value of sst imaging in the clinical follow-up, in particular in those lesions with positive sst2 immunostaining. Negativity for sst2, however, does not rule out tracer uptake in some patients, with heterogeneous sst2 expression within the tumor as a potential explanation.