68ga-dotanoc and Digestive-System-Neoplasms

In the past few years, the introduction of novel PET tracers labelled with (68)Ga has changed the diagnostic approach to neuroendocrine tumours (NET) in specialized centres. Although somatostatin analogue tracers labelled with (111)In have represented the gold standard imaging modality for NET detection in past decades, the advantages offered by both labelling somatostatin analogues with (68)Ga and using PET/CT tomography for image acquisition, account for the increasing use of these tracers in clinical practice. There are an increasing number of reports of the higher accuracy of (68)Ga-DOTA peptide PET/CT for the detection of NET lesions as compared to morphological imaging procedures and somatostatin receptor scintigraphy. Moreover, the use of (68)Ga-DOTA peptides offers the possibility to noninvasively evaluate NET cells for the presence of somatostatin receptor expression, with direct therapeutic implications. Several practical advantages also favour the use of (68)Ga-DOTA peptides including the relatively easy and economic synthesis process and the fact that (68)Ga labelling can be performed in centres without an on-site cyclotron. We describe the advantages and limitations of (68)Ga-DOTA peptide PET/CT imaging for the assessment of gastroenteropancreatic NET referring to the available literature as well as to our experience, and finally highlight potential future perspectives.

Topics: Digestive System Neoplasms; Gallium Radioisotopes; Heterocyclic Compounds, 1-Ring; Humans; Multimodal Imaging; Neuroendocrine Tumors; Organometallic Compounds; Peptides; Positron-Emission Tomography; Radiopharmaceuticals; Tomography, X-Ray Computed

Somatostatin receptor PET tracers such as [(68)Ga-DOTA,1-Nal(3)]-octreotide ((68)Ga-DOTANOC) and [(68)Ga-DOTA,Tyr(3)]-octreotate ((68)Ga-DOTATATE) have shown promising results in patients with neuroendocrine tumors, with a higher lesion detection rate than is achieved with (18)F-fluorodihydroxyphenyl-l-alanine PET, somatostatin receptor SPECT, CT, or MR imaging. (68)Ga-DOTANOC has high affinity for somatostatin receptor subtypes 2, 3, and 5 (sst2,3,5). It has a wider receptor binding profile than (68)Ga-DOTATATE, which is sst2-selective. The wider receptor binding profile might be advantageous for imaging because neuroendocrine tumors express different subtypes of somatostatin receptors. The goal of this study was to prospectively compare (68)Ga-DOTANOC and (68)Ga-DOTATATE PET/CT in the same patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and to evaluate the clinical impact of (68)Ga-DOTANOC PET/CT.. Eighteen patients with biopsy-proven GEP-NETs were evaluated with (68)Ga-DOTANOC and (68)Ga-DOTATATE using a randomized crossover design. Labeling of DOTANOC and DOTATATE with (68)Ga was standardized using a fully automated synthesis device. PET/CT findings were compared with 3-phase CT scans and in some patients with MR imaging, (18)F-FDG PET/CT, and histology. Uptake in organs and tumor lesions was quantified and compared by calculation of maximum standardized uptake values (SUVmax) using volume computer-assisted reading.. Histology revealed low-grade GEP-NETs (G1) in 4 patients, intermediate grade (G2) in 7, and high grade (G3) in 7. (68)Ga-DOTANOC and (68)Ga-DOTATATE were false-negative in only 1 of 18 patients. In total, 248 lesions were confirmed by cross-sectional and PET imaging. The lesion-based sensitivity of (68)Ga-DOTANOC PET was 93.5%, compared with 85.5% for (68)Ga-DOTATATE PET (P = 0.005). The better performance of (68)Ga-DOTANOC PET is attributed mainly to the significantly higher detection rate of liver metastases rather than tumor differentiation grade. Multivariate analysis revealed significantly higher SUVmax in G1 tumors than in G3 tumors (P = 0.009). This finding was less pronounced with (68)Ga-DOTANOC (P > 0.001). Altogether, (68)Ga-DOTANOC changed treatment in 3 of 18 patients (17%).. The sst2,3,5-specific radiotracer (68)Ga-DOTANOC detected significantly more lesions than the sst2-specific radiotracer (68)Ga-DOTATATE in our patients with GEP-NETs. The clinical relevance of this finding has to be proven in larger studies.

Topics: Adult; Aged; Aged, 80 and over; Cross-Over Studies; Digestive System Neoplasms; Female; Gallium Radioisotopes; Humans; Male; Middle Aged; Multimodal Imaging; Neuroendocrine Tumors; Organometallic Compounds; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Receptors, Somatostatin; Tomography, X-Ray Computed

Therapy with the somatostatin analogue DOTA-(0)-Phe(1)-Tyr(3)-octreotide (DOTATOC) labeled with a beta-(DOTA-Phe-Tyr-Octreotide) emitter such as 90Y or 177Lu is accepted for the palliative treatment of unresectable neuroendocrine cancer. However, the optimal route of administration has not been determined. Using positron-emission tomography (PET)-labeled 68Ga-DOTATOC, we compared selective tumoral uptake on PET/computed tomography (CT) after arterial or venous administration of the agent in patients with gastroenteropancreatic neuroendocrine tumor.. Fifteen patients with neuroendocrine cancer were examined with 68Ga-DOTATOC PET/CT after intravenous (i.v.) and intraarterial (i.a.) administration within 4 weeks of each other and without any intervening therapy. Eleven patients had multifocal metastases, six were considered to have unresectable primary tumor. The intraarterial catheter was placed in the vessel supplying the main tumor burden. The standard uptake value (SUV) was used to compare intratumoral concentrations of 68Ga-DOTATOC.. Compared with i.v. infusion, the i.a. infusion resulted in an increased SUV in 117 of 122 (96%) liver metastases. The average increase in SUV was 3.75-fold higher with i.a. administration. The increase in uptake for the primary tumors was dependent on the selectivity of the catheter placement, resulting in variable increases in SUV after i.a. injection (1.44- to 7.8-fold higher).. This study showed that uptake of DOTATOC is commonly several fold higher after selective i.a. administration in comparison with i.v. injection in both the primary tumor as well as in liver metastases of neuroendocrine cancer. Therefore, intraarterial DOTATOC is a promising drug for regionally intensified radiopeptide therapy.

Topics: Adult; Aged; Digestive System Neoplasms; Female; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Male; Middle Aged; Neuroendocrine Tumors; Organometallic Compounds; Positron-Emission Tomography; Radiopharmaceuticals; Radiotherapy; Tomography, X-Ray Computed

Neuroendocrine tumors (NET) are known for an overexpression of somatostatin receptors (SSTR). In light of very few and partially contradictory publications, the present study aims to achieve a definite immunohistochemical (IHC) quantification and assessment of the distribution of all five SSTR-subtypes on NET and to evaluate an implementable scoring system, comparing the immunoreactive score of Remmele and Stegner (IRS) to the Her2-score. In 21 patients 40 different tumor tissues were IHC analysed using polyclonal antibodies for SSTR1 and 3-5 and the monoclonal antibody UMB-1 for SSTR2A. SSTR expression was quantitatively evaluated according to HER2-score and IRS, correlated among each other and to the maximum standardized uptake value (SUVmax) in tumor lesions as measured by PET/CT using 68Ga-DOTA-NOC.. According to the IRS, the expression of SSTR2A and 3 predominated equally with 84%, followed by SSTR4 (44%) and SSTR1 and 5 (32%). With the Her2-scoring system the most frequent subtype was found to be SSTR2A (68%), followed by SSTR3 (64%), SSTR1 (44%), SSTR5 (40%), and SSTR4 (36%). The IRS-classification and the Her2-score were found to be statistically comparable, and their correlation is highly significant for each SSTR assessment (p<0.01).. The results of the analyses revealed heterogeneous expression patterns. SSTR2A and 3 were highly expressed, demonstrating the importance of SSTR for diagnostics and therapy. Relatively high frequency of SSTR3 and 4 on NET give reasons to try pansomatostatin analogues for therapy rather than concentrating only on the SSTR2A. Statistically, none of the immunohistochemical scores was superior. However, due the heterogeneity of the cytoplasmic staining justice we propose the IRS as a uniform scoring scheme for IHC NET diagnostic.

Topics: Biomarkers, Tumor; Digestive System Neoplasms; Humans; Immunohistochemistry; Ki-67 Antigen; Multimodal Imaging; Neuroendocrine Tumors; Organometallic Compounds; Positron-Emission Tomography; Predictive Value of Tests; Prognosis; Radiopharmaceuticals; Receptor, ErbB-2; Receptors, Somatostatin; Retrospective Studies; Tomography, X-Ray Computed