Somatostatin Analogues for Somatostatin-Receptor-Mediated Radiotherapy of Cancer

Abstract

The aim of the present study was to selectively target a β-emitter-labelled octreotide analogue to somatostatin (SRIF)-receptor-expressing tumours and to evaluate the feasibility of SRIF-receptor-mediated radiotherapy by delivering a lethal dose of radiation to the tumour. The most promising compound in a series of DTPA-coupled octreotide analogues was DTPA-benzyl-acetamido-D-Phe¹, Tyr³ctreotide (SDZ413). In vitro, SDZ413 binds with nanomolar affinity to SRIF-receptors (IC50 = 4.0 nM) and inhibits growth hormone release from primary cultures of rat pituitary cells with an IC₅₀ of 7.2 nM. Biodistribution studies with [⁹⁰Y]SDZ413 demonstrated a fast and significant SRIF-receptor-specific accumulation of the labelled conjugate (tumour/muscle ratio after 24 h: 52/1). [⁹⁰Y]SDZ413 was effective in the radiotherapy of SRIF-receptor-positive tumours in a nude mouse model. A single treatment with [⁹⁰Y]SDZ413 led to a significant decrease (25%) of tumour mass. This effect was mediated by the intact radioligand, since treatment with [⁹⁰Y]SDZ978, a derivative of SDZ413 which does not bind with high affinity to SRIF-receptors or with the unlabelled SDZ413 alone, failed to affect tumour growth. These results suggest that receptor-targeted radiotherapy with a ⁹⁰Y-labelled octreotide analogue represents a new strategy for the treatment of SRIF-receptor-positive tumours that have been previously diagnosed with OctreoScan®¹¹¹ (pentetreotide).

Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Tumors – Well-Differentiated Jejunal-Ileal Tumor/Carcinoma

“…Targeting these receptors with radiolabeled somatostatin analogs may not only be used for imaging but also for radiotherapy. Since the early 1990s, different radiolabeled analogs have been used for tumor-targeted therapy [94][95][96][97] . For metastatic disease with evidence of expression of sst2 as demonstrated by SRS, two still FDA-and EMEA-unapproved analogs for peptide receptor radionuclide therapy (PRRT) - 90 Y-DOTA-octreotide [98][99][100][101][102][103][104][105][106][107][108][109] and 177 Lu-DOTA-octreotate (Lutate) [110][111][112][113] -show promising results.…”

Guidelines for the Diagnosis and Treatment of Neuroendocrine Gastrointestinal Tumours

“…Targeting these receptors with radio-labelled somatostatin analogues may be used not only for imaging but also for radiotherapy [106][107][108][109][110] . Since 1992, different analogues have been investigated for somatostatin receptor radionuclide therapy (SRRT) [111][112][113][114][115][116][117][118][119] .…”

Receptor-mediated radiotherapy with 90Y-DOTA-D-Phe1-Tyr3-octreotide

“…In addition to neuroendocrine tumours, SS receptors have been identified on cancers of the central nervous system [2], breast [3], lung and lymphatic tissue [4], and the use of radionuclide-labelled SS analogues shows promise for therapy as well as diagnosis of such cancers [5]. Moreover, sst2 receptors have been observed in peritumoural vessels [6,7], thus enabling an anti-angiogenetic response during radionuclide therapy.…”