19617743

Multimodality Imaging in a Patient With Adrenocortical Carcinoma Leading to Peptide Receptor Radionuclide Therapy

Kim Francis Andersen, MD,* Anders Mellemgaard, MD,¡ and Helle Westergren Hendel, MD, PhD*

Abstract: In the recommended staging system for adrenocortical carcinoma, nuclear medicine modalities are optional. In cases of distorted postoperative anatomy and when postoperative infection/inflammation mimics malig- nancy, functional imaging is helpful. We present a case of a patient with adrenocortical carcinoma where F-18 FDG dual time point imaging and somatostatin receptor scintigraphy were used in the diagnostic work up after surgery complicated by infection, until end-stage palliative peptide receptor radionuclide therapy. The estimated uptake on somatostatin receptor scin- tigraphy is traditionally done visually on planar images. We suggest a more objective, semiquantitative approach by comparing the tumor uptake with a standard reference.

Key Words: multi modality imaging, adrenocortical carcinoma, radionuclide therapy, somatostatin receptor, OctreoScan

(Clin Nucl Med 2009;34: 543-548)

Received for publication January 8, 2009; accepted April 7, 2009.

From the Departments of *Clinical Physiology and Nuclear Medicine, and tOncol- ogy, Herlev Hospital, University Hospital of Copenhagen, Herlev, Denmark.

Reprints: Kim Francis Andersen, MD, Department of Clinical Physiology and Nuclear Medicine, Herlev Hospital, University Hospital of Copenhagen, DK-2730, Herlev, Denmark. E-mail: kifran02@heh.regionh.dk.

Copyright @ 2009 by Lippincott Williams & Wilkins ISSN: 0363-9762/09/3408-0543

REFERENCES

1. Hustinx R, Smith RJ, Benard F, et al. Dual time point fluorine-18 fluorode- oxyglucose positron emission tomography: a potential method to differentiate malignancy from inflammation and normal tissue in the head and neck. Eur J Nucl Med. 1999;26:1345-1348.

2. Uesaka D, Demura Y, Ishizaki T, et al. Evaluation of dual-time-point 18F-FDG PET for staging in patients with lung cancer. J Nucl Med. 2008;49:1606-1612.

3. Zhuang H, Pourdehnad M, Lambright ES, et al. Dual time point 18F-FDG PET imaging for differentiating malignant from inflammatory processes. J Nucl Med. 2001;42:1412-1417.

4. Guillermet-Guibert J, Lahlou H, Cordelier P, et al. Physiology of somatostatin receptors. J Endocrinol Invest. 2005;28(suppl international):5-9.

5. Green S, Weiss GR. Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria. Invest New Drugs. 1992;10:239-253.

6. Kwekkeboom DJ, Bakker WH, Kam BL, et al. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled soma- tostatin analogue [177Lu-DOTA(0), Tyr3]octreotate. Eur J Nucl Med Mol Imaging. 2003;30:417-422.

7. Teunissen JJ, Kwekkeboom DJ, de Jong M, et al. Peptide receptor radionuclide therapy. In: Biersack H-J, Freeman LM, eds. Clinical Nuclear Medicine. 1st ed. New York, NY: Heidelberg-Berlin; 2007:443-55.

FIGURE 1. A 43-year-old woman underwent primary left-sided nephrectomy due to a large (10 cm in diameter) nonfunction- ing adrenocortical carcinoma (ACC). The surgery was considered microscopically irradical. PET/CT scans 7 and 11 months af- ter surgery were normal, though, a small lesion was seen on the CT scan close to the spleen. PET scan (Philips Gemini TF, 60 minutes p.i. of 340 MBq [9.2 mCi]) F-18 FDG) 15 months after surgery showing multiple retroperitoneal tumors in the tumor bed (region of the former left kidney), in a superior phrenic lymph node, and in a splenic focus (not visualized on the CT scan). An attempt at radical surgery with abdominal splenectomy and excision of the metastases, that turned out to invade the thoraco-abdominal diaphragm, was done. The operation was complicated by perforation and necrosis of the colon (the lienal flexure), perforation of the thoraco-abdominal diaphragm, and development of an abscess in the left fossa (tumor bed).

[WB_CTAC] Body 26-10-2007

15 cm

H

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Series: 880550 / Slice: 1

F

unitless LL:0.00 UL:3284.00

PT: [WB_CTAC] Body

PT: [WB_CTAC] Body

CT: Body-Low Dose CT

CT: Body-Low Dose CT PT: 13-11-2007 CT: 13-11-2007

PT: 13-11-2007

CT: 13-11-2007

5 cm

6 cm

Min: 1.3-SUV Mac: 10.2 SUV Mean: 3.2-SUV Diameter 30.00 mm

MÆ1.15WW

Olameter: 30.00 mm

MỐNG - 467 HU

Mean: 19HU

PT Series: 624130 / Slice: 57 CT Series: 2 / Slice: 57

Etter 30.00mm

L

PT Series: 591520 / Slice: 58

19:00 mm

CT Series: 2 / Slice: 58

SUV LL:0.00’UL:7.06

SUV LL:0.00 UL:6.51 Width:350 Level:35

Width:350 Level:35

SUV 60 min p.i.	Spleen	Lymph node	Aorta	SUV 120 min p.i.	Spleen	Lymph node	Aorta
Max	8.4	6.5	2.2	Max	10.2	7.1	2.1
Min	1.1	0.9	1.1	Min	1.2	0.7	1.2
Mean	3.0	1.7	1.7	Mean	3.2	1.8	1.6

FIGURE 2. Three months later the patient was referred to PET/CT for a baseline study. Because of the described abscess in the left fossa and persistent leucocytosis, dual time point imaging was made to try to differentiate infection from malignancy as a possible cause of PET-positive foci. The scan visualized high uptake in multiple foci in the tumor bed and in an enlarged superior phrenic lymph node. SUVmax, min, and mean were measured in a volume of 3 cm in diameter 60 minutes (left panel) and 120 minutes (right panel) p.i. in the region of the resected spleen, in the left superior phrenic lymph node, and in the abdominal aorta repre- senting the background activity. The increasing SUV values in the foci increased the suspicion of malignancy.1-3

FIGURE 3. As ACCs could express somatostatin receptors (SSTR1-SSTR5), predominantly SSTR2,4 the patient was referred to soma- tostatin receptor scintigraphy (SRS) to confirm the suspicion of malignancy seen on the PET scan and to evaluate the indication for pal- liative treatment in terms with peptide receptor radionuclide therapy (PRRT). However, In-111 DTPAOC whole-body scintigraphy 4 hours p.i. of 122 MBq (3.3 mCi) In-111 DTPAOC (Philips Forte dual-head gamma camera, scan speed 8 cm/min, matrix 256 × 256, MEGP collimator with energy windows 170 keV ± 20% and 247 keV ± 20%) visualized no focal uptake in the tumor bed. The circular focus of low In-111 DTPAOC uptake in the resected spleen fossa, best seen on the posterior view, represents the gastric fundus. Consequently, the possibility of successful radionuclide therapy was regarded minute due to the pronounced mismatch between F-18 FDG PET and the SRS. Consequently, the patient was offered chemotherapy, which was terminated after 2 series because of malignant progression including appearance of lung metastases on a chest CT scan.

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FIGURE 4. Another SRS was made to re-evaluate the possibility of PRRT. Static anterior image of the abdominal region re- corded with SPECT/CT approximately 5 hours p.i. of 156 MBq (4.2 mCi) In-111 DTPAOC (Philips Precedence SPECT/CT 16 Power configuration, view time 262 seconds/1,000,000 counts, matrix 256 x 256, MEGP collimator with energy window 245 keV ± 10%) showed focal high uptake in the left lobe of the liver, the region of the resected spleen/left kidney, and several foci in relation to the left-sided abdominal wall. No foci were visualized in the lungs. Grading of the uptake on the SRS was done visually on a 4-point scale.5,6 The metastases in the liver and the tumor bed both were characterized as grade 3 tumors.

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TABLE 1	Nb. Pixel	Tot. Counts	Max	Min	Mean
ROI 1	532	221641	8649.0	8.0	416.6
ROI 2	494	31971	104.0	22.0	64.7
ROI 3	682	35229	90.0	18.0	51.7
ROI 4	207	3297	34.0	2.0	15.9
ROI 5	299	6650	39.0	11.0	22.2

FIGURE 5. To estimate tumor uptake objectively, a semiquantitative approach by comparing the tumor uptake with a standard reference was made by placing a standard reference (black) of 9 MBq (243 µCi) In-111 DTPAOC at the same level (measured on transaxial CT scan) as the metastases in the liver (orange) and the region of the resected spleen/left kidney (tumor bed) (blue). The standard reference was covered with PMMA glass to simulate human tissue. The number of pixels and counts were registered and used for quantitative calculation of uptake of the radiolabeled somatostatin analog, which turned out to be 0.74% (liver) and 0.71% (tumor bed) of the standard reference, respectively. The semi-quantitative SRS now matched the dual time point PET scan, and thus confirmed the extent of tumor recurrence. It was concluded that the patient fulfilled the recommended selection criterion for palliative treatment in terms of PRRT (177Lu-DOTATOC).7 The patient was then referred to another institution for DOTATOC treatment. Following an infusion of arginine and lysine, 7.4 GBq (200 mCi) of 177Lu-DOTATOC was administered. Scintigrams the following day showed uptake in areas of the liver and multiple sites in the abdomen. In the following days, an episode of atrial fi- brillation and melena was observed. Further DOTATOC treatment was planned, but the patient’s general condition worsened pro- gressively, and she died before any evaluation of the treatment was performed.