PET/CT comparing 68Ga-DOTATATE and other radiopharmaceuticals and in comparison with CT/MRI for the localization of sporadic metastatic pheochromocytoma and paraganglioma

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Abstract

Pheochromocytomas/paragangliomas (PPGLs) and their metastases are tumors that predominantly express somatostatin receptor 2 (SSR2). (68)Ga-DOTA(0)-Tyr(3)-octreotate ((68)Ga-DOTATATE) is a PET radiopharmaceutical with both high and selective affinity for SSRs. The purpose of this study was to evaluate the utility of (68)Ga-DOTATATE in comparison with other specific and nonspecific radiopharmaceuticals recommended in the current guidelines for the localization of metastatic sporadic PPGL by PET/CT.

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Jean Claude Reubi, B. Waser, J Laissue … (2001)

Somatostatin receptors are known to be expressed in a large number of human tumours and represent the basis for in vivo tumour targeting. Stable somatostatin derivatives such as octreotide or lanreotide are the most frequently used radiopharmaceuticals acting through specific binding to somatostatin receptors; however, they do not bind with high affinity to all five receptor subtypes. Whereas the mRNAs for most receptor subtypes have been detected in tumours, it is in most cases unclear which of the receptor subtype proteins are expressed. Since in vitro receptor binding methods are close correlates and predictors of in vivo peptide receptor targeting, we took advantage of the recently developed subtype-selective analogues and evaluated approximately 200 tumours for their receptor subtype protein expression in specific binding assays using autoradiography with 125I-[Leu8, D-Trp22, Tyr25]-somatostatin-28 and displacement by subtype-selective analogues. The majority of the tested neuroblastomas, meningiomas, medulloblastomas, breast carcinomas, lymphomas, renal cell carcinomas, paragangliomas, small cell lung carcinomas and hepatocellular carcinomas predominantly expressed sst2. The prostate carcinomas and sarcomas preferentially expressed sstl, while a majority of inactive pituitary adenomas displayed sst3 and, to a lesser extent, sst2. Growth hormone-secreting pituitary adenomas preferentially expressed sst2 and sst5; gastroenteropancreatic tumours and phaeochromocytomas frequently displayed sst2 and/or sstl. Non-neoplastic human tissues such as vessels, nerve plexus, pancreatic islets, prostatic stroma, adrenal medulla, spleen and germinal centres of the lymphoid tissues preferentially expressed sst2. However, the human gastric mucosa predominantly expressed sst1 while colonic mucosa displayed sst2. Interestingly, a minority of tumours showed a strong 125I-[Leu8, D-Trp22, Tyr25]-somatostatin-28 binding, of which less than 50% could be displaced by the sum of the five subtype-selective analogues. This observation suggests the existence of an as yet unknown subtype in selected tumours. This study is the first report to analyse the somatostatin receptor subtype expression in tumours with binding methods. We conclude that sst2, with high affinity for current radiopharmaceuticals such as Octreoscan, is predominantly expressed in a majority of tumours. Fewer tumour types (sarcomas, prostate cancers, inactive pituitary adenomas) preferentially express another subtype. This information is of importance with regard to the clinical applications and development of somatostatin analogues with distinct receptor subtype selectivities.

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Chemotherapy with cyclophosphamide, vincristine and dacarbazine for malignant paraganglioma and pheochromocytoma: systematic review and meta-analysis.

N Niemeijer, G Alblas, L. T. van Hulsteijn … (2014)

Chemotherapy with cyclophosphamide, vincristine and dacarbazine (CVD) can be used for palliative treatment of malignant pheochromocytoma and paraganglioma. However, the precise effect of this chemotherapeutic regimen on tumour volume is unclear. The main objective of this study was to perform a systematic review and meta-analysis assessing the effect of chemotherapy with CVD on tumour volume in patients with malignant paraganglioma/pheochromocytoma.