Lymphomas are malignant tumours of the immune system. Lymphomas are classified as Hodgkin or non-Hodgkin lymphomas with several subtypes. In Finland the amount of newly diagnosed Hodgkin lymphomas is 120-150 new cases per year and it accounts for 12 % of all lymphomas. Non-Hodgkin lymphoma is the sixth most common cancer in men and the eight most common cancer in women in Finland. There are approximately 1200 new cases per year and the incidence has been increasing during the last decade (1, 2).
Etiology of lymphomas is mostly unknown but many risk factors have been identified. Diagnostics and classification to different subgroups is based on clinical, pathological, molecular, and radiological studies. Some of lymphomas subtypes can be cured with current treatment methods, however, many of them remain still incurable (1). Clearly, more accurate diagnostic tools with subsequent targeted therapies against lymphomas are needed.
Somatostatin receptors (SSTs) are expressed by a wide variety of different tumour cell types, including malignant lymphomas (3-6). Somatostatin receptor imaging by octreotide scintigraphy has showed a sensitivity of 95-100 % in Hodgkin lymphoma and 80 % in non-Hodgkin lymphoma. However, somatostatin receptor scintigraphy does not appear to have a significant role in diagnostic process because of the relatively low uptake of the used somatostatin analogue (oktreotide) and limited sensitivity of the single photon emission computed tomography (SPECT) acquisition to detect and localise small involved nodes (6, 7). Hence, somatostatin receptor imaging has been further developed with the advent of hybrid SPECT and positron emission tomography (PET) and computed tomography (CT) scanners. Several other radioligands have been studied to improve the binding affinity(8) . This has also offered a new target for tumor cell-specific therapy using different somatostatin analogs labelled with therapeutic radionuclides such as 90Y-DOTATOC, a somatostatin receptor subtype 2 (SST2) -specific ligand. Clinical studies of peptide receptor radionuclide therapy (PRRT) have extensively focused on neuroendocrine tumors as a palliative treatment modality (9-11). Another new candidate for SST based imaging and treatment is 68Ga-DOTANOC, a high-affinity ligand of somatostatin receptor subtypes 2, 3 and 5 (SST2, SST3, SST5) (12). Neuroendocrine tumors are known to express SST2 and they show high uptake of radiolabeled somatostatin analogs on PET. However, lymphomas may mimick NETs on DOTANOC PET/CT as was shown in a recent case report (13). Therefore, further studies on SST2 status and DOTANOC uptake are in order to establish the role of peptide based imaging in diagnosis and possible PRRT in lymphomas.
The aim of the study is to determine tumor uptake of 68Ga-DOTANOC in patients with non-Hodgkin and Hodgkin lymphoma to characterize the SST2, SST3 and SST5 receptor status of the tumour in vivo with 68Ga-DOTANOC PET/CT. In addition, immunohistochemical analysis of SST2, SST3 and SST5 subtype status will be made of the tumor specimens obtained in routine diagnostic biopsy resection. Furthermore, we will correlate PET findings with advanced MRI techniques, such as diffusion weighted imaging (DWI) in an attempt to find methods which limit radiation exposure especially in young patients. Hence, PET/CT will be performed with 68Ga-DOTANOC and 18F-FDG and compared with whole-body MRI (including DWI) to define the most sensitive and specific imaging method appropriate for routine diagnosis and follow-up of patients with lymphoma.
To our knowledge, no prospective studies comparing octreodite analogue based PET/CT imaging with standard diagnostic procedures have been published until now. PET/CT offers a clear advantage over scintigraphy in terms of sensitivity and resolution which should be helpful in determining the SST status of various histologic forms of lymphomas We hypothesize that a positive 68Ga-DOTANOC PET/CT scan correlates with the overexpression of all or some SST subtypes in lymphomas, which is possibly linked to a more indolent behavior of the disease. Furthermore, we hypothesize that 68Ga-DOTANOC PET/CT imaging provides a valid method to select patients with lymphoma for radionuclide therapy with 177Lu-DOTATATE. Third, differential diagnosis with NETs may also improve after receiving information on SST status in lymphomas. Thus findings in our study may be useful not only for biologic characterization but also for diagnosis and management of these heterogenous diseases originating in the lymphatic system