Preoperative localization of a gastrin ~ secreting tumour by total 11 body imaging with 1 Indium ~ labelled pentatreotide

HALI, A HENDLER, B TAYLOR, S WOLMAN. PreoP.erative localization of a gastrin-secreting tumour by total body imaging with Indium-labelled pentatreotide. Can J Gastroenterol 1994;8(3):189-192. A 41-year-old female presented with persistent diarrhea, and was diagnosed with Zollinger-Ellison syn<lrome when her gastrin level was greater than 3000 ng/L. All modalities for preoperative localization of her gastrinomu were unsuccessful, including transabdominal and endoscopic ultrasound, computed tomography, pancreatic angiogram, selective cranshepatic portal venous sampling and magnetic resonance imaging. The gastrin-secreting tumour was visualized using the somatoscatin analogue pentatreotide labelled with Jndium, combined with gamma camera imaging. A successful resection of the tumour resulted in the normalization of serum gastrin levels 3 .S years after presentation. A discussion of the merits and sensitivities of these tests for preoperative localization of gastrin-secreting tumours will be presented.

P REOPERATIVE LOCALIZATION OF gastrinomas followe<l by surgical resection is the procedure of choice for gastrin-secreting tumours.C urrent imaging techniques, including ultrasound, computed tomographic scan, angiography and selective venous sampling, identify only 50% of tumour sites (1 ).Endoscopic ultrasound has recently become popular, but its sensitivity is limited to pancreatic and lumenal . 1111 <l' 'd d' sites.
n 1um-pcntatreot1 e, a ra 10labelled somatostatin analogue, can be used to perform total body scanning for primary and metastatic sites of neuroen<locrine tumours expressing somatostatin receptors such as gastrinomas.This noninvasive imaging method should be considere<l after computed tomography an<l ultrasound fail to locate the tumour.

CASE PRESENTATION
A 41 -year-old female presented to a gastroenterologist fi ve months after the onset of progressively worsening diarrhea.She had a perianal fistula and inguinal hernia repair within the past few months and had been on antibiotics.Diarrhea consisted of 12 watery, nonbloody bowel movements per day.There was urgency but no tenesmus, and mild abdominal cramping was relieved by bowel movements.Avoid-A1.Ic?1al l'imagerie par resonance magnctique.La tumeur secretrice Jc gastrine a etc v1sualisee a l'aidc Jc !'analogue de la somatostatine pcntatreo tide marque a Colonoscopy was cnmpletcly normal to the cecum.Ciastro~copy showcJ a norma l esophagus, but mcx~erate to severe gastritis in the antrum and severe duodenttis.l11e patient was prescribed misoprostol 200 µ g qid and diphenoxylate.Two months later, she continued to have symptoms and was referred to the auth1)rs' centre for further investtgat ion.At referral the patient had experienced a weight loss of 6.8 kg.Further history revealed diarrhea occurred despite a dice of clear fluids or fasting in preparatton for endoscopic investiga-tions.Stool vo lume~ were l .6 to 2.0 L in 24 h collections.lnvcstigaLions revealed the fo llowing data.Red blood cell fo lace and vitamin 81 z levels were normal.A bile acid breach test was negattve.Iron, ionized calci um, carotene , urine van illylmandelic acid and 5-hydroxyindnleacetic acid, prolactin, growth hormone, intact parathyroid hormone and morning cortisol levels were all normal.Calciconin was less than 8 pmol/L (normal less than 15).The patient's gasrrin level, however, was 3150 ng/L (nonnal less than 90).A diagnosis of Zollinger-Ellison syndrome was made.The pattenr was treated for symptoms, successfully at first, with omeprazole 20 mg hid; somatostatin 200 µ g tid was added when the diarrhea returned, but this did nm prcxluce any change in the diarrhea.Later rhe patient required as much as omeprazolc 80 mg hid to control the diarrhea.
Imagmg studies were mitiared co locate a gastrinoma.Computed tomography of al:xlomen, chest x-ray and ultrasou nd were performed in duplicate and were read as negative fo r mass lesions.Repeat gastroscopy (seven months after the first) showed scattered erosive hemorrhagic are;is in the stomach and duodenum, with enlarged folds and nigae consistent with a gastrin hypersecrctory state.Pancreatic angiogram failed to reveal any tumour.Transhepatic portal venous sampling did not provide meaningful data which could have located ,1 tumo ur.M;ignetic resonance imaging did not show any mass lesions.Repeat gastrin level testing (two years after the first) was 23 74 ng/L.Repeat gastroscopy showed normal mucosa except for prominent rugae.
Based on reports in the literature, ;in c1ttempt was made by the rad ioph;irmacy in the authors' hospital to attach a radioiodine label to commercially available octreotide (2,3 ).This was not successful because of in;idequate bindmg of the radiolabel.
Recently, an indium-labelled somatostatin analogue -111 Indium-pentatreotide (octreoscan I 11 , Ma linckrodt) -was made available for mvestigational use.A request made by the authors co the I lea lth Protection Branch for emergency release of the compound was granted.The patient was given an intravenous injection of pentatreotide reconstituted with 12.3 mBq 111 Indium-chloride.
Boch whole body planar (Figure 1) and si ngle phown emission computed tomography (SPECT) images of rhe abdomen (Figure 2) were obtame<l with ;in Elscint gam ma camera (l laifa, Israel) at 4 h, and planar images a lone were obtai ned at 24 h.The images demonstrated an intense focus of abnormal activity ante rior to the lower pole of rhe k idney, and the abnormality reportedly was located either in the Lail of the pancreas or nearby.
Based on the 111 Indium-penrntreoude scan, the p;iuent was taken to la-parot0my.lntraopcrative ultrasound confirmed chat the mass was in the small bowel mesentery, not the pancreas.There was no evidence of another primary site.A 3 cm mass was resec ted and patho logically confirmed as a gastrinoma.Follow-up gascrin levels, one and two mo nths after surgery, were 80 a nd 56 ng/L, respec tively.The patient is no longer o n medications, and is asymptomatic.He r gascrin levels will be followed every three months fo r the first yea r.

DISCUSSION
Soma cosca tin inhibits secre tion in various nc uroendocrine t issues, in addition to its likely role as a neurotransmitter.Tumours from cells naturally conta mmg somatostatin receptors often continue to express vary ing concentrations of somatostatin recepto rs, such as pituitary and isle t cell tumours.In addition, some wmours not n awrally containing somatostatin receptors may a lso occasionally do so, no doubt as part of malignant transformation.Examples of these arc meningiomas a nd breast carc inomas ( 4 ).Somatostatin adm inistercd as therapy may relieve symptoms of tumour hypersecretion , and it has been shown to inhibit tumour growth (5,6 ).
Gastrinomas are ofte n diffic ult to loca l izc by conventiona l techniques if they arc less than 2 c m in size -unfortunately they ofte n are sma ller (7), and only 50% of tumo urs are found with commonly used imaging procedures (8) .Since tumours are difficult to find, and patie nts are be ing treated with more potent ac id-inhibiting pharmaceutical formu la tions (Hz blockers, proton pump inhibitors), pa tients are presenting la ter with me tastatic disease more ofte n than they are with ulcer complications ( l ).S ixty pe r cent of gastrinomas a re malignant, and metastatic gastrinoma carries a 20 to 40% five-year surviva l (1 ,9, 10).Therefo re, although symptoma tic control has improved, tumour localization for resection before progression to metasta tic disease is still vita l.The morta lity associated with metastases is high and patients often go on to an exploratory laparotomy despite a lack of localizing info rmation provide d by conventional investigation.lntraope ra tive ultrasound combined with palpation improves the sensiti vity of finding the tumour ( 11), yet 40% of gastrinomas  In the past 20 years, a numbe r of imaging techniques h ave tried to localize gastrinomas preoperatively.Initia lly abdomina l ultrasound and computed tomography we re employed, but the ir sensitivity relates to tumour size.In one study looking at islet cell tumours ranging in size from 0. 7 to 2.0 c m, computed tomography visua lized seven of 16 tumours, and ultrasound nine of 15.Sensitivity decreased with tumours in the tail of the panc reas (14).In another study, the sensitivi ty of ultrasound to detect extrahepatic gastrinomas was 20% and that of computed tomography was 45% (15 ).Magnetic resonance imaging is even less sensitive than ultrasound and computed tomography (1 5 ).lf the tumour is not localized, pa ncreatic angiography and transhepatic selec tive venous sampling have been advocated.More recently, endoscopic ultrasound has shown promise.lrs sensitivity exceeds that of angiography.
Rosch 's study (4) in 1992 showed that 82% of pancrea tic ne uroendocrine tumours not fo und by con ventiona l ultrasound and computed tomography were localized by e ndoscopic ultrasound.
Angiography can localize tumours 30 to 40% of the ti me ( 1,8).T ranshepatic venous sampling has a 70 to 90% sensitivity, but onl y for tumours in the duodenum or pancreas ( 16).Furthermore, t he corre la tion be twe en hormone gradient a nd tumour localization, eg, head versus ta il of pancreas, has a sensitiv ity of 35%.The 111 Indium-pentatreotide scan has the pote ntial of a nonin vasive method to localize tumours and provides the advantage o f pic king up metasta tic disease in tumours contai ning somatosta tin receptors (2,3 ).It appears that growth ho rmone pituitary adcnomas, meningiomas, carc inoid tumours, gastrinomas, and some cases of breast carc inomas and insulinomas are most likely to conta in somatostatin receptors (2,4 ).O f these, gastrinomas can be extrapancreatic 30 to 40% of the t ime (8,13,17).Duodenal and gastric sites may be visualized by experienced endoscopists with ul trasound.H oweve r, peripanc reatic and periduoden al lymph nodes may be more difficult to locate.

CONCLUSIONS
Since the expertise fo r this procedure is not yet readily ava il able, the 111! cl" .dn 1um-penta treot1 e scan combines t he advantages of localizing tumours fa r from the endoscopist's and an giographer's v iew with a n easily administe red and noninvasive test in a nuclear medic ine fac il icy.In Lamberts' study (3 ), seve n of nine pa ncreatic endocrine tumours we re v isualized.Larger studies a re needed to evaluate sen sitivity and specific ity fo r this procedure.N evertheless, because it is non invasive and can scan the whole body, t his technique provides signi ficant advantages over oth er invest igative me thods.W e conclude t ha t

Figure 2 )
Figure2) T ransaxial single photon emission computed tomography ( Sf'ECT) images of the gastrinoma us ing11 1 Indium-/)entatreotide.The tumour (arrow) is localized anterior co the lower /Joie of the left kidney 111 Indium-pentatreotide imaging should be considered fo r gastrino mas (or any tu mour expressing soma-C AN J GASTROENTEROL V OL 8 No 3 MAY/JUNE 1994 Au et al tostatin receptors) as the localization study to follow an unhelpful ultrasound and computed tomography scan.