Molecular imaging as in vivo molecular pathology for gastroenteropancreatic neuroendocrine tumors: implications for follow-up after therapy.
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 (90)Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid(0) (DOTA),Tyr(3)-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 [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-DOTATATE), with disappearance of (111)In-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 (177)Lu-DOTATATE but subsequently relapsed with many receptor-negative metastases, requiring intensive chemotherapy.


CONCLUSIONS
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.
Krenning
Eric P
EP
Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. E.P.Krenning@erasmusmc.nl
Valkema
Roelf
R
Kwekkeboom
Dik J
DJ
de Herder
Wouter W
WW
van Eijck
Casper H J
CH
de Jong
Marion
M
Pauwels
Stanislas
S
Reubi
Jean-Claude
JC
D000368:Aged; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology / Q000379:methods; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D010455:Peptides / Q000627:therapeutic use; D010818:Practice Patterns, Physicians'; D011379:Prognosis; D011868:Radioisotopes; D011877:Radionuclide Imaging / Q000379:methods; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D010455:Peptides; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D013004:Somatostatin