Intraoperative detection of somatostatin-receptor-positive neuroendocrine tumours using indium-111-labelled DTPA-D-Phe1-octreotide

Wängberg, Bo; Forssell-Aronsson, Eva; Tisell, Lars‐Erik; Nilsson, Ola; Fjälling, Martha; Ahlman, Håkan

doi:10.1038/bjc.1996.134

Cited by 34 publications

(33 citation statements)

References 14 publications

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“…The 111 In concentration was high in tumour tissues. It was frequently higher in liver metastases in comparison with the primary tumour, which we have previously observed in patients with other types of neuroendocrine tumours [13,22,23]. The concentration in bile was very high, due to the short time interval after injection of the radiopharmaceutical and the fast excretion of a small fraction of the radiopharmaceutical via this pathway [24].…”

Section: Discussionmentioning

confidence: 78%

“…Studies Using 111 In-DTPA-D-Phe 1 -Octreotide Twenty-four hours prior to surgery, the patient received 190 MBq 111 In-DTPA-D-Phe 1 -octreotide (10 Ìg) (Mallinckrodt Medical BV, Petten, The Netherlands) by intravenous injection and tumour localization was performed by scintigraphy preoperatively [13]. To study tissue 111 In activity concentration, tumour and normal tissue samples were excised.…”

Section: Assay Of Histaminementioning

confidence: 99%

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Gastric Carcinoid with Histamine Production, Histamine Transporter and Expression of Somatostatin Receptors

Kölby¹,

Wängberg²,

Ahlman³

et al. 1998

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A case of sporadic, histamine-producing gastric carcinoid with liver metastases is reported. The patient was treated with somatostatin analogue (octreotide) combined with cortisone and blockade of histamine receptors prior to surgery, which included subtotal gastrectomy, excision of lymph node metastases and superficial liver metastases. Residual liver metastases were injected with ethanol. These interventions markedly reduced the urinary excretion of the main histamine metabolite (MeImAA). Eighteen months later combined immuno- and chemotherapy was initiated due to tumour progression and recurrent hormonal symptoms with good clinical results over 12 months. Scintigraphy, using ¹¹¹In-DTPA-D-Phe¹-octreotide, visualized somatostatin receptors (sstr) in primary tumour, lymph node metastases and liver metastases. The tissue/blood ¹¹¹In concentration ratios of tumour biopsies were very high. Northern analyses confirmed expression of all subtypes of sstr_1–5. Immunocytochemically, tumour cells were strongly positive for chromogranin A, histamine and vesicular monoamine transporter (VMAT) 2 (histamine transporter), but negative for VMAT 1, suggesting an origin from gastric enterochromaffin-like cells. In primary tumour cell cultures, histamine, 5-HTP and 5-HIAA, but not 5-HT, could be detected in conditioned culture medium, indicating a defective decarboxylation of the tryptamine precursor. This rare case of histamine-producing gastric carcinoid demonstrates that excellent symptom relief can be achieved despite disseminated disease, if active, multimodal treatment strategy is instituted. The presence of high numbers of sstr in tumour tissue also raises the possibility of receptor-guided radiotherapy.

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Section: Discussionmentioning

confidence: 78%

Section: Assay Of Histaminementioning

confidence: 99%

Gastric Carcinoid with Histamine Production, Histamine Transporter and Expression of Somatostatin Receptors

Kölby¹,

Wängberg²,

Ahlman³

et al. 1998

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“…Octreotide treatment of BON cells for 4 days increased the secretion of 5-HT by 27% but reduced the secretion of 5-HIAA by 54%. Figure ratios in carcinoid tumours compared with other neuroendocrine tumours, for example medullary thyroid carcinoma (ForssellAronsson et al, 1995;Wangberg et al, 1996;Ahlman et al, 1997;Tisell et al, 1997). In general, the T/B ratios seemed to be somewhat lower in primary tumours and lymph node metastases than in liver metastases.…”

Section: Somatostatin Receptor Scintigraphy and T/b 1111n Activity Comentioning

confidence: 96%

Comparative studies on the expression of somatostatin receptor subtypes, outcome of octreotide scintigraphy and response to octreotide treatment in patients with carcinoid tumours

Nilsson

Kölby²,

Wängberg³

et al. 1998

Br J Cancer

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SummaryWe have compared the expression of somatostatin receptor (sstr) subtypes with the outcome of somatostatin receptor scintigraphy and the effect of somatostatin receptor activation in patients with disseminated carcinoid tumours. Tumour tissues from nine patients with midgut carcinoids (ileal) and three patients with foregut carcinoids (gastric, thymic) were analysed using Northern blotting. Expression of somatostatin receptors was demonstrated in all tumours (12 out of 12), with all five receptor subtypes present in 9 out of 12 tumours. Somatostatin receptor scintigraphy using [1111n]DTPA-D-Phe1-octreotide visualized tumours in all patients (12 out of 12). The "'in activity concentrations in tumour tissue (T) and blood (B) were determined in three tumours 1-7 days after injection of the radionuclide. The T/B 1111n activity concentration ratios ranged between 32 and 651. Clinically, treatment with the long-acting somatostatin analogue octreotide resulted in marked symptom relief accompanied by a significant reduction in tumour markers, for example urinary-5-HIAA levels (28-71% reduction).Incubation of midgut carcinoid tumours in primary culture with octreotide (10 gM) resulted in a reduction in spontaneously secreted serotonin (45-71% reduction) and 5-HIAA (41-94% reduction). The results demonstrate that carcinoid tumours possess multiple somatostatin receptor subtypes and that somatostatin analogues such as octreotide, which preferentially bind to somatostatin receptor subtype 2 and 5, can be used in the diagnosis and medical treatment of these tumours. In the future, novel somatostatin analogues with subtype specific receptor profiles may prove to be of value for individualizing the treatment of disseminated carcinoid tumour disease.

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“…carcinoid metastases in the mesenteric root after lymph node dissection). Promising results have been reported, but scintillation detection is clearly not sensitive enough to detect microscopic tumour growth or microadenomas [46]. …”

Section: Interventional Treatment Of Liver Metastasesmentioning

confidence: 99%

Interventional Treatment of Gastrointestinal Neuroendocrine Tumours

et al. 2000

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Neuroendocrine (NE) tumours of the gastrointestinal tract (carcinoids and endocrine pancreatic tumours) are rare diseases. In the presence of liver metastases these patients may suffer from disabling symptoms due to hormone overproduction. Patients with localized disease can be resected for cure and also patients with liver metastases can undergo potentially curative tumour resection. However, long-term follow-up of the latter cases indicates frequent recurrence of tumour. Using close biochemical monitoring of tumour markers combined with newer techniques for tumour visualization, these recurrences can often be diagnosed at an early stage so that repeat surgical procedures can be performed. During the last years very active surgery has been recommended for NE tumours, many of which have a relatively slow growth. Even in patients not amenable to curative liver surgery, debulking can be considered if the main tumour burden can be safely excised. The primary aim of this type of treatment is palliation of hormonal symptoms. An important question is whether the aggressive treatment actually prolongs survival. No prospective studies have been performed. Such studies are hampered by the lack of strict surgical programs running over long periods and the relative rarity of NE tumours. Liver transplantation may be another treatment modality in selected cases.

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Intraoperative detection of somatostatin-receptor-positive neuroendocrine tumours using indium-111-labelled DTPA-D-Phe1-octreotide

Cited by 34 publications

References 14 publications

Gastric Carcinoid with Histamine Production, Histamine Transporter and Expression of Somatostatin Receptors

Gastric Carcinoid with Histamine Production, Histamine Transporter and Expression of Somatostatin Receptors

Comparative studies on the expression of somatostatin receptor subtypes, outcome of octreotide scintigraphy and response to octreotide treatment in patients with carcinoid tumours

Interventional Treatment of Gastrointestinal Neuroendocrine Tumours

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