Metaiodobenzylguanidine and somatostatin in oncology: role in the management of neural crest tumours

Hoefnagel, Cornelis A.

doi:10.1007/bf00173045

Cited by 126 publications

(107 citation statements)

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“…Radiolabelled MIBG allows the scintigraphic imaging of neural crest tumours (Weiland et al, 1980) and ['311]MIBG is used in the treatment of neuroblastoma and phaeochromocytoma (Hartmann et al, 1987;Mastrangelo, 1987;Schwabe et al, 1987;Voute et al, 1988). Clinical experience since 1984 has demonstrated its potential, with an objective response rate of 35% in patients with progressive heavily pretreated disease (Hoefnagel, 1994). Clinical studies are now evaluating the role of ['311]MIBG at an earlier stage in therapy, either as a first line treatment or in combination with other treatment modalities (DeKraker et al, 1995;Gaze et al, 1995;Mastrangelo et al, 1995).…”

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confidence: 99%

Toxicity to neuroblastoma cells and spheroids of benzylguanidine conjugated to radionuclides with short-range emissions

Cunningham

Mairs²,

Wheldon³

et al. 1998

Br J Cancer

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Summary Radiolabelled meta-iodobenzylguanidine (MIBG) is selectively taken up by tumours of neuroendocrine origin, where its cellular localization is believed to be cytoplasmic. The radiopharmaceutical [1311]MIBG is now widely used in the treatment of neuroblastoma, but other radioconjugates of benzylguanidine have been little studied. We have investigated the cytotoxic efficacy of beta, alpha and Auger electronemitting radioconjugates in treating neuroblastoma cells grown in monolayer or spheroid culture. Using a no-carrier-added synthesis route, we produced 1231-, 1251-, 1311-and 211At-labelled benzylguanidines and compared their in vitro toxicity to the neuroblastoma cell line SK-N-BE(2c) grown in monolayer and spheroid culture. The Auger electron-emitting conjugates ([1231]MIBG and [1251]MIBG) and the alpha-emitting conjugate ([211At]MABG) were highly toxic to monolayers and small spheroids, whereas the beta-emitting conjugate [1311]MIBG was relatively ineffective. The Auger emitters were more effective than expected if the cellular localization of MIBG is cytoplasmic. As dosimetrically predicted however, [211At]MABG was found to be extremely potent in terms of both concentration of radioactivity and number of atoms ml-' administered. In contrast, the Auger electron emitters were ineffective in the treatment of larger spheroids, while the beta emitter showed greater efficacy. These findings suggest that short-range emitters would be well suited to the treatment of circulating tumour cells or small clumps, whereas beta emitters would be superior in the treatment of subclinical metastases or macroscopic tumours. These experimental results provide support for a clinical strategy of combinations ('cocktails') of radioconjugates in targeted radiotherapy.Keywords: meta-iodobenzylguanidine; neuroblastoma; tageted radiotherapy; astatine Meta-iodobenzylguanidine (MIBG) is a structural analogue of the neuroadrenergic blocking drugs bretylium and guanethidine. It is selectively accumulated by an active mechanism in cells of neural crest origin. Radiolabelled MIBG allows the scintigraphic imaging of neural crest tumours (Weiland et al, 1980) and ['311]MIBG is used in the treatment of neuroblastoma and phaeochromocytoma (Hartmann et al, 1987;Mastrangelo, 1987;Schwabe et al, 1987;Voute et al, 1988). Clinical experience since 1984 has demonstrated its potential, with an objective response rate of 35% in patients with progressive heavily pretreated disease (Hoefnagel, 1994). Clinical studies are now evaluating the role of ['311]MIBG at an earlier stage in therapy, either as a first line treatment or in combination with other treatment modalities (DeKraker et al, 1995;Gaze et al, 1995;Mastrangelo et al, 1995).Although many patients show beneficial responses to ['311]MIBG treatment, a significant number subsequently relapse from previously undetected tumour sites (Sisson et al, 1989). This suggests that microtumours below the limit of clinical detectability have survived ['311]MIBG therapy. A possible explanation for the rela...

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confidence: 99%

Toxicity to neuroblastoma cells and spheroids of benzylguanidine conjugated to radionuclides with short-range emissions

Cunningham

Mairs²,

Wheldon³

et al. 1998

Br J Cancer

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“…Patients should be taken off these drugs for an appropriate time prior to scintigraphy. To control hypertension, a-blockers (such as phenoxybenzamine) or b-blockers (such as propranolol) can be administered (50). To minimise free radioiodine thyroidal uptake, pretreatment with SSKI or Lugol's solution is given (47 -49).…”

Section: Patient Preparation and Mibg Scintigraphic Techniquementioning

confidence: 99%

“…There are a number of series on the use of MIBG scintigraphy in other neuroendocrine tumours, especially medullary thyroid carcinoma (MTC) and carcinoid (50,61). With regard to MTC, there are two different indications for MIBG scintigraphy.…”

Section: Other Clinical Applications Of Mibg Scintigraphymentioning

confidence: 99%

“…The second indication concerns the use of MIBG scintigraphy in the post-surgical follow-up of MTC patients with increased calcitonin and/or carcino-embryonic antigen (CEA) levels to visualise metastatic foci of MTC; unfortunately, a rather low sensitivity, ranging from 33 to 45% has been reported in these patients, particularly for detection of liver tumour deposits (61). For the same clinical purpose, other radiotracers such as 201 thallium chloride, Tc-(V)-DMSA (olimercaptosuccinic acid), anti-CEA monoclonal antibodies, 99m Tc-methoxy-isobutyl-isonitrile and 111 In-octreotide have shown sensitivity rates superior to MIBG, ranging from 65 to 85% (50,61,63,64). As with MTC, the sensitivity of MIBG scintigraphy in carcinoid patients is less than ideal, with reported values ranging from 30 to 60% (50,61).…”

Section: Other Clinical Applications Of Mibg Scintigraphymentioning

confidence: 99%

“…For the same clinical purpose, other radiotracers such as 201 thallium chloride, Tc-(V)-DMSA (olimercaptosuccinic acid), anti-CEA monoclonal antibodies, 99m Tc-methoxy-isobutyl-isonitrile and 111 In-octreotide have shown sensitivity rates superior to MIBG, ranging from 65 to 85% (50,61,63,64). As with MTC, the sensitivity of MIBG scintigraphy in carcinoid patients is less than ideal, with reported values ranging from 30 to 60% (50,61).…”

Section: Other Clinical Applications Of Mibg Scintigraphymentioning

confidence: 99%

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Functional scintigraphy of the adrenal gland

et al. 2002

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Over the last 30 years nuclear medicine imaging of the adrenal gland and its lesions has been achieved by the exploitation of a number of physiological characteristics of this organ. By seeking and utilising features which are quantitatively or qualitatively different from those of the adjacent tissues, functional depiction of the adrenal gland and its diseases, which in most cases retain the basic physiology of their tissue of origin, including both the cortex and the medulla, are now a useful clinical reality. Agents widely used in clinical practice include: (a) uptake and storage of radiolabelled cholesterol analogues via the low density lipoprotein (LDL) receptor and cholesterol ester storage pool in the adrenal cortex ( 131 I-6-b-iodomethyl-norcholesterol, 75 Se-selenomethyl-norcholesterol); (b) catecholamine type I, presynaptic, uptake mechanism and intracellular granule uptake and storage mechanism in the adrenal medulla and extra-adrenal paraganglia ( 131 I-, 123 I-and 124 Imeta-iodo-benzyl-guanidine (MIBG), 18 F-metafluoro-benzyl-guanidine); (c) cell surface receptor binding of peptides/neurotransmitters/modulators such as for the family of five subtypes of somatostatin receptors ( 123 I-tyr-octreotide, 111 In-DTPA-octreotide, 111 In-DOTA-octreotide and many others); (d) although not specific for the adrenal gland, increased glycolysis by tumours, particularly the most malignant varieties, 18 F-2-fluoro-D-deoxyglucose can thus be expected to depict certain malignant lesions such as malignant pheochromocytomas (particularly the minority which are not detected by MIBG) and adrenal incidentalomas (particularly when they occur in patients with known extraadrenal malignancies). There are a variety of adrenal tissue characteristics with potential for exploitation but which are not currently in clinical use, and which may, nevertheless, have potential as imaging agents. These include: (a) inhibitors of adrenal cortical steroid hormone synthesis enzymes (e.g. radiolabelled analogues of metyrapone); (b) radiolabelled lipoproteins which bind to adrenocortical LDL receptors; (c) inhibitors of catecholamine biosynthesis enzymes (e.g. radiolabelled analogues of tyrosine and related amino acids); (d) cell surface receptors for various peptides and hormones which may be overexpressed on adrenal cortical or adrenal medullary tumours (e.g. radiolabelled analogues of ACTH on adrenocortical cells of zona fasciculata or zona glomerulosa origin, neurotransmitter/hormone message peptides binding to cell surface receptors such as bombesin, vasoactive intestinal polypeptide, cholecystokinin and opiate peptides); (e) the adrenal cortex can also synthesise cholesterol ab initio from acetate, and preliminary studies with 11 C-acetate positron emission tomography have shown interesting results. European Journal of Endocrinology 147 13-28 Adrenal cortexThe adrenal cortex is constituted of three layers. The outer layer, the glomerulosa zone, produces mineralocorticoids (mainly aldosterone) under the control of the renin -a...

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Radioisotope-guided surgery in patients with pheochromocytoma and recurrent medullary thyroid carcinoma

Adams

Lorenz

et al. 2001

Cancer

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BACKGROUND The objective of this study was to appraise the detection of metastases of medullary thyroid carcinoma (MTC) and pheochromocytoma using radioguided surgery (RGS) and to compare the results with external imaging modalities, surgical palpation, and histopathologic findings. METHODS Twenty‐five patients with recurrent MTC underwent preoperative scintigraphic imaging with 500 megabecquerels (MBq) of technetium 99m(V)‐dimercaptosuccinic acid [99mTc(V)‐DMSA] and 222 MBq of indium 111 (111In)‐pentetreotide. The radiopharmaceutical that showed the greatest preoperative tumor uptake was selected for intraoperative RGS. Surgery was performed 24 hours after the administration of 111In‐pentetreotide or 4 hours after the injection of 99mTc(V)‐DMSA. Furthermore, three male patients underwent surgery who suffered from recurrent pheochromocytoma (injection of 180 MBq iodine 123‐labeled metaiodobenzylguanidine [123I‐MIBG] 4–5 hours before surgery). RESULTS Overall, lesion detection sensitivities in patients with MTC for computed tomography, 111In‐pentetreotide, and 99mTc(V)‐DMSA were 32%, 34%, and 65%, respectively. Surgical palpation identified lymph node metastases of recurrent MTC with a sensitivity of 65%, whereas RGS localized 64 malignant lesions (sensitivity, 97%). Altogether, 71 lesions could be excised, 5 of which were adjudged false positive with respect to MTC metastases. Both surgical palpation and RGS localized all paravertebral subdiaphragmatic lesions (size ≥ 2 cm) of recurrent pheochromocytoma seen in the preoperative MIBG scan. CONCLUSIONS RGS was capable of localizing more and smaller metastases of MTC compared with conventional imaging modalities and surgical palpation. However, the relatively high radioligand accumulation in the kidneys (111In‐pentetreotide) and the dense hepatic and biliary signals using MIBG limited their use for intraoperative detection of tumors in the area of the adrenal gland. Cancer 2001;92:263–70. © 2001 American Cancer Society.

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Metaiodobenzylguanidine and somatostatin in oncology: role in the management of neural crest tumours

Cited by 126 publications

References 37 publications

Toxicity to neuroblastoma cells and spheroids of benzylguanidine conjugated to radionuclides with short-range emissions

Toxicity to neuroblastoma cells and spheroids of benzylguanidine conjugated to radionuclides with short-range emissions

Functional scintigraphy of the adrenal gland

Radioisotope-guided surgery in patients with pheochromocytoma and recurrent medullary thyroid carcinoma

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