111In-Pentetreotide

Description

¹¹¹In-Pentetreotide (also known by brand names such as Octreoscan^®, ¹¹¹In-DTPA-Octreoscan™ Neuroendomedix^®, ¹¹¹In-DTPA-Phe1-Octreotide, ¹¹¹In-DTPA-OC, and SomatoTher^® in its therapeutic version) is a radiopharmaceutical developed and marketed by Mallinckrodt Pharma / Curium. It is an ¹¹¹In-labeled somatostatin analogue used primarily for diagnostic imaging of neuroendocrine tumors (NETs). The base, non-labeled peptide linked with DTPA, is referred to as Pentetreotide, with alternate designations like DTPA-SMS, MP-1727, SDZ-215811s, and Sdz-215-811.

The term Pentetreotide describes a modified version of the Octreotide peptide that is conjugated to a DTPA linker. Octreotide itself is a synthetic peptide marketed as Sandostatin^®. DTPA (diethylenetriamine pentaacetic acid), also known as pentetic acid, serves as a chelating agent to bind the radioactive Indium-111 isotope. It is important to note that the terms ¹¹¹In-Pentreotide and ¹¹¹In-Pentatreotide are common misspellings.

Clinical Applications

¹¹¹In-Pentetreotide is a diagnostic agent used to target and image tumors that express somatostatin receptors. The parent peptide, Octreotide, is an octapeptide analog of the natural hormone somatostatin, but with enhanced potency and resistance to enzymatic degradation. Somatostatin is a peptide hormone produced in the hypothalamus and pancreas that inhibits the secretion of growth hormone, insulin, glucagon, and gastrin. Since somatostatin receptors are present on various neuroendocrine and certain non-neuroendocrine tumors, this imaging agent can localize tumors and assess their spread.

The diagnostic use of ¹¹¹In-Pentetreotide involves imaging neuroendocrine tumors (NETs), including but not limited to:

• Pancreatic endocrine (islet cell) tumors (e.g., gastrinoma, insulinoma, glucagonoma, VIPoma)
• Carcinoid tumors
• Small cell lung carcinomas
• Neuroblastomas
• Pheochromocytomas
• Paragangliomas
• Medullary thyroid carcinoma
• Pituitary tumors
• Certain non-NET cancers, including Hodgkin’s and non-Hodgkin’s lymphomas, certain brain tumors (like meningiomas and astrocytomas), Merkel cell tumors of the skin, granulomatous diseases (like sarcoidosis), and breast cancer.

The typical administered dose of ¹¹¹In-Pentetreotide for imaging is 3–6 mCi, and it has been shown to detect over 84% of neuroendocrine tumors. It is often more effective than MIBG (metaiodobenzylguanidine) for identifying gastroenteropancreatic neuroendocrine tumors (GEP-NETs), though MIBG remains superior for detecting pheochromocytomas. The use of somatostatin receptor imaging is generally reserved for patients with suspected metastatic disease, especially when PET imaging is unavailable.

Toxicity and Safety

The primary target organ for toxicity is the kidney, so the use of ¹¹¹In-Pentetreotide in patients with renal impairment should be approached with caution. The standard dose per patient is around 6 mCi, and renal function should be monitored to reduce the risk of adverse effects.

Availability and Pricing

¹¹¹In-Pentetreotide is marketed under the brand name Octreoscan^® by Mallinckrodt Pharma / Curium. It was granted US marketing authorization in June 1994 but is now out of patent. In Russia, the agent is available from Pharm Sintez under the name Oktreotid.

Pricing for ¹¹¹In-Pentetreotide has fluctuated significantly over time. In the 2010s, a 3 mCi dose cost around $1,500 (EUR 1,300) in the US. In 2014, the official sales price in the EU was approximately EUR 1,034 (about US$ 1,150), but most doses were sold at an average price of EUR 900-950 (US$ 1,000-1,100) worldwide. Patient charges could reach up to EUR 2,000. By 2020, the price of a dose in the US had risen sharply to around $6,500. Despite its previous commercial success, revenues from Octreoscan declined after 2015, falling from an estimated $87M annually. This decline is attributed to competition from new imaging agents, particularly ⁶⁸Ga-labeled NET tracers like Soma-Kit®.

Competition

¹¹¹In-Pentetreotide faces intense competition from newer somatostatin analogues. Early competitors included agents labeled with SPECT radionuclides like ^99mTc and ¹¹¹In, but the most significant threat now comes from PET radionuclides like ⁶⁸Ga and ⁶⁴Cu. These agents offer higher resolution imaging and lower radiation exposure to patients.

The introduction of ⁶⁸Ga-DOTATATE and ⁶⁸Ga-DOTATOC as PET tracers, as well as the advent of therapeutic agents like ¹⁷⁷Lu-Lutathera^®, has greatly reduced the demand for ¹¹¹In-Pentetreotide. In 2018, ¹⁷⁷Lu-Lutathera became the first therapeutic somatostatin analogue to gain market approval, offering both therapeutic and diagnostic solutions via theranostic pairs (e.g., ⁶⁸Ga-DOTATATE for imaging and ¹⁷⁷Lu-DOTATATE for treatment). These advancements have dramatically impacted sales of Octreoscan^®, as most NET patients now undergo PET imaging rather than SPECT imaging.

Comments

Octreoscan^® was once a key tool in imaging neuroendocrine tumors, but it now faces obsolescence due to the superior performance and availability of ⁶⁸Ga-based PET tracers and ¹⁷⁷Lu-based therapies. ⁶⁸Ga-DOTATATE and ⁶⁸Ga-DOTATOC provide better imaging clarity, lower radiation doses, and faster scan times, making them the preferred choice in regions where PET imaging is available.

The market for ¹¹¹In-Pentetreotide has seen a significant shift. While Curium continues to manufacture the product, its use is expected to dwindle as alternatives like ⁶⁸Ga-DOTATATE and ¹⁷⁷Lu-Lutathera® become more widely adopted. One attempt to repurpose ¹¹¹In-Pentetreotide as a therapeutic agent through Auger electron emission was not successful. For Auger electrons to be effective, the emitter must be positioned near the DNA within the nucleus of the cell—a requirement that ¹¹¹In-Pentetreotide could not reliably achieve. Consequently, therapeutic alternatives like ⁹⁰Y-DOTATOC and ¹⁷⁷Lu-DOTATATE are now preferred for treating neuroendocrine tumors.

Without significant price increases or exclusive demand in areas lacking PET infrastructure, the future of ¹¹¹In-Pentetreotide as a viable product is uncertain.