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Molecular Imaging as In Vivo Molecular Pathology for Gastroenteropancreatic Neuroendocrine Tumors: Implications for Follow-Up After Therapy

¹ Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
² Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
³ Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands
⁴ Department of Nuclear Medicine, Université Catholique de Louvain, Brussels, Belgium
⁵ Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Bern, Switzerland

Peptide receptor scintigraphy in combination with anatomic imaging methods such as CT can be regarded as molecular imaging. It offers insight into the variability of somatostatin receptor expression in neuroendocrine tumor lesions within a patient. The somatostatin receptor status of all tumors in a patient is an important issue, because receptor-negative lesions may be poorly differentiated and characterized by aggressive growth and poor prognosis, with consequences for the choice of therapy. Methods: Follow-up studies of 3 patients with gastroenteropancreatic neuroendocrine tumors who had been previously treated with peptide receptor radionuclide therapy (PRRT) are presented. Results: Patient 1 had a mixed response after treatment with ⁹⁰Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid⁰ (DOTA),Tyr³-octreotide. The response included fibrosis and a low rate of mitosis in receptor-positive lesions that had decreased in volume after treatment and vital tumor cells and a high rate of mitosis in receptor-negative lesions that had grown since the start of treatment. Patient 2 had a good clinical and biochemical response after PRRT with [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate (¹⁷⁷Lu-DOTATATE), with disappearance of ¹¹¹In-pentetreotide uptake on follow-up scans, whereas on CT the size of the lesions remained unchanged, possibly indicating tumor necrosis. Patient 3 had a complete remission after PRRT with ¹⁷⁷Lu-DOTATATE but subsequently relapsed with many receptor-negative metastases, requiring intensive chemotherapy. Conclusion: Although biopsy is required for initial diagnosis and treatment planning, noninvasive molecular imaging may evolve into in vivo molecular pathology in selected groups of patients, especially in treatment follow-up.

Key Words: neuroendocrine tumor • pathology • peptide • peptide receptor radiation therapy

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