Somatostatin Receptor 2–Targeting Compounds

Abstract

The molecular imaging and treatment of neuroendocrine tumors (NETs) with radiolabeled somatostatin analogs represent a milestone in the development of theranostic compounds. Whole-body scintigraphy with 111 In-pentetreotide has revolutionized the diagnosis and staging of NETs and the evaluation of treatment outcomes. At present, diagnostic accuracy with positron-emitting radionuclides is greater than 90%. Peptide receptor radionuclide therapy (PRRT) has become a well-accepted treatment for patients with welldifferentiated inoperable or metastatic NETs and disease progression after first-line treatment. Disease control rates (complete or partial remission or stable disease in patients with formerly progressive disease) of up to 95%, with a low incidence of long-term hematologic and renal toxicity, have been reported. In a recently published randomized trial, compared with intensified treatment of midgut NETs with longacting and repeatable octreotide, PRRT reduced the hazard of disease progression and death by 79%. Upcoming developments in PRRT include the use of somatostatin receptor antagonists and a-emitting radionuclides, which may further enhance treatment outcomes.

Theranostik von neuroendokrinen Tumoren

“…SSAs stimulieren Somatostatinrezeptoren (SSTRs) auf der Oberfläche von neuroendokrinen Tumorzellen, was zu einer Verringerung der Freisetzung von Hormonen aus den Tumorzellen führt. Im Menschen existieren 5 Subtypen des Somatostatinrezeptoren, wobei v. a. der Subtyp 2 (SSTR2) von neuroendokrinen Tumoren exprimiert wird [4,21]. Somatostatinanaloga sind metabolisch deutlich stabiler als der natürliche Rezeptorligand, das Peptidhormon Somatostatin, und deshalb wesentlich einfacher als Therapeutika anzuwenden.…”

“…Die SPECT-Bildgebung mit 111 In-DTPA-Octreotid wurde in den letzten 10 -15 Jahren in den meisten Ländern durch die PET mit 68 Ga-markierten Octreotidanaloga ersetzt [21]. Grund dafür waren nicht nur die höhere Sensitivität und räumliche Auflösung der PET gegenüber der SPECT, sondern auch die verbesserten pharmakologischen Eigenschaften der 68 Ga-markierten Verbindungen [21]. Klinisch werden v. a. die 3 Liganden Tyrosin-Octreotid (TOC), Tyrosin-Octreotat (TATE) und Napthylalanin-Octreotid (NOC), jeweils gekoppelt an den Chelator DOTA eingesetzt.…”

“…Der Chelator DOTA erlaubt neben der Markierung mit dem diagnostischen Nuklid 68 Ga auch die Markierung mit den therapeutischen Beta-Emittern 177 Lu und 90 Y [21]. Die Verbindungen 90 Y-DOTAT-TOC, 177 Lu-DOTA-TATE und 177 Lu-DOTA-TOC wur-den in einer Reihe von Phase II-Studien seit 2000 getestet und an verschiedenen Zentren auch klinisch eingesetzt.…”

Design and development of the theranostic pair 177Lu‐OPS201/68Ga‐OPS202 for targeting somatostatin receptor expressing tumors

“…Thus, peptide analogs of the endogenous ligand somatostatin with high affinity for sstr can be used for targeting NET cells in vivo. Over the years, such optimized peptide structures in terms of in vivo stability, affinity, specificity, and pharmacokinetics led to radiopharmaceuticals for imaging and treatment of sstr‐expressing tumors . Nowadays, sstr imaging (scintigraphy or positron emission tomography [PET]) using somatostatin analogs labeled with γ‐emitters (eg, 111 In) or β + ‐emitters (eg, 68 Ga or 64 Cu), respectively, plays an important role in the detection of the primary tumor, staging, restaging, and assessment of treatment response in patients with NETs .…”

“…Over the years, such optimized peptide structures in terms of in vivo stability, affinity, specificity, and pharmacokinetics led to radiopharmaceuticals for imaging and treatment of sstr-expressing tumors. 2,3 Nowadays, sstr imaging (scintigraphy or positron emission tomography [PET]) using somatostatin analogs labeled with γ-emitters (eg, 111 In) or β + -emitters (eg, 68 Ga or 64 Cu), respectively, plays an important role in the detection of the primary tumor, staging, restaging, and assessment of treatment response in patients with NETs. 2,4 Importantly, it can distinguish patients who qualify and may benefit from peptide receptor radionuclide therapy (PRRT) with these analogs labeled with β − -emitters (eg, 177 Lu or 90 Y) 4 or more recently α-emitters (eg, 213 Bi or 225 Ac).…”