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

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

Eric P. Krenning, MD, PhD¹^,2, Roelf Valkema, MD, PhD¹, Dik J. Kwekkeboom, MD, PhD¹, Wouter W. de Herder, MD, PhD², Casper H.J. van Eijck, MD, PhD³, Marion de Jong, PhD¹, Stanislas Pauwels, MD, PhD⁴ and Jean-Claude Reubi, MD, PhD⁵

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

View larger version (32K):

[in a new window]

FIGURE 1. (A) Upper and lower panels represent transverse CT, SPECT, and hematoxylin and eosin histology of somatostatin receptor (SSR)-positive tumor 2 and SSR-negative tumor 1, respectively, in patient 1, after 4 cycles of PRRT. (B) Sizes of 4 hepatic lesions after PRRT with somatostatin analog ( ${blacktriangleup}$ ). Tumors above stippled line were not seen on octreotide scan, nor were the 2 tumors below this line; one of each was biopsied and depicted in (A).

View larger version (110K):

[in a new window]

FIGURE 2. Histopathology and receptor autoradiography of somatostatin receptor (SSR)-negative tumor 1 (A, B, C, D) and SSR-positive tumor 2 (E, F, G, H) in patient 1. Hematoxylin and eosin staining (A, E), ¹²⁵I-Tyr³-octreotide autoradiography (B, C, G, F) in absence (B, F) and presence (C, G) of excess of unlabeled octreotide, and MIB1 immunohistochemistry (D, H).

View larger version (57K):

[in a new window]

FIGURE 3. Scans acquired 3 d after first (left) and second (right) injection of 7.4 GBq ¹⁷⁷Lu-DOTATATE in patient 2, diagnosed with liver metastases of a NET.

View larger version (27K):

[in a new window]

FIGURE 4. (A) CT scans before (left), 3 mo after (middle), and 12 mo after (right) last therapy with ¹⁷⁷Lu-octreotate in patient 3 with liver metastases of an operated neuroendocrine pancreatic tumor. Disappearance of tumor sites (arrows, left) at 3-mo follow-up (middle). Recurrence of tumors at 12-mo follow-up (right). (B) Planar scans of abdomen, 3 d after injection of 7.4 GBq ¹⁷⁷Lu-octreotate (left and middle) and 1 d after the injection of 222 MBq ¹¹¹In-octreotide. Image at 3 d shows clear accumulation in tumor sites in liver after first therapy (left) and loss of intensity of uptake in liver lesions after last therapy (middle). Octreotide scan at 3-mo follow-up was negative (right). (C) Course of chromogranin A (CgA; normal upper limit, 100 ng/mL) and neuron-specific enolase (NSE; normal upper limit, 16.3 µg/L) during and after ¹⁷⁷Lu-octreotate therapy and chemotherapy.