[111In-DTPA-D-Phe1]-octreotide, a potential radiopharmaceutical for imaging of somatostatin receptor-positive tumors: synthesis, radiolabeling and in vitro validation

doi:10.1016/0024-3205(91)90052-D

Life Sciences

Volume 49, Issue 22, 1991, Pages 1583-1591

https://doi.org/10.1016/0024-3205(91)90052-D Get rights and content

Abstract

Somatostatin receptor-positive human tumors can be detected using radioiodinated analogues of somatostatin, both in vitro and in vivo. [¹²³I-Tyr³]-octreotide has been successfully used in the visualization of somatostatin receptor-positive tumors by gamma camera scintigraphy, but this radiopharmaceutical has some major drawbacks, which can be overcome with other radionuclides such as ¹¹¹In. As starting material for a potentially convenient radiopharmaceutical, a diethylenetriaminopentaacetic acid (DTPA) conjugated derivative of octreotide (SMS 201–995) was prepared. This peptide, [DTPA-D-Phe¹]-octreotide (SDZ 215-811) binds more than 95 % of added ¹¹¹In in an easy, single-step labeling procedure without necessity of further purification. The specific somatostatin-like biologic effect of these analogues was proven by the inhibition of growth hormone secretion by cultured rat pituitary cells in a dose-dependent fashion by octreotide, [DTPA-D-Phe¹]-octreotide and non-radioactive [¹¹⁵In-DTPA-D-Phe¹]-octreotide. The binding of [¹¹¹In-DTPA-D-Phe¹]-octreotide to rat brain cortex membranes proved to be displaced similarly by natural somatostatin as well as by octreotide, suggesting specific binding of [¹¹¹In-DTPA-D-Phe¹]-octreotide to somatostatin receptors. The binding of the indium-labeled compound showed a somewhat lower affinity when compared with the iodinated [Tyr³]-octreotide, but indium-labeled [DTPA-D-Phe¹]-octreotide still binds with nanomolar affinity. In conjunction with in vivo studies, these results suggest that [¹¹¹In-DTPA-D-Phe¹]-octreotide is a promising radiopharmaceutical for scintigraphic imaging of somatostatin receptor-positive tumors.

References (15)

S.W.J. Lamberts et al.
Bailliére's Clinical Endocrinology and Metabolism
(1990)
E.P. Krenning et al.
Lancet
(1989)
W. Bauer et al.
Life Sci
(1982)
J.C. Reubi et al.
Life Sci
(1981)
J.C. Reubi
Life Sci
(1985)
W.H. Bakker et al.
Life Sci
(1991)
S.W.J. Lamberts et al.
J Clin Endocrinol Metab
(1990)

There are more references available in the full text version of this article.

Cited by (334)

Positron emission tomography and single-photon emission computed tomography physics
2022, Handbook of Neuro-Oncology Neuroimaging
Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are becoming increasingly important for the diagnosis and staging of brain tumours, as well as for the monitoring of response to therapy. The purpose of these imaging modalities is to estimate the distribution of a radiotracer from external measurements of the pattern of photons emerging from the brain. In this chapter, the physics underlying the generation of these photons will be described. A great deal of effort has been expended in the design of SPECT and PET instrumentation, leading to major advances in this area. The major scanner configurations, as well as the instrument design considerations, are discussed. Images must be mathematically reconstructed from the external measurements; the techniques used to accomplish this whilst correcting for physical effects that degrade the accuracy and precision of the measurements are outlined.
Imaging the immune cell in immunotherapy
2022, NK Cells in Cancer Immunotherapy: Successes and Challenges
The clinical success of cancer immunotherapy and the challenges currently limiting its further application to treat more cancer types have highlighted the pivotal role played by molecular imaging.
In this chapter, we will discuss the following topics:
- (1)
  Imaging objectives from an immunological perspective
- (2)
  Imaging modalities and labeling strategies for cancer immunotherapy
- (3)
  Application of the Imaging Toolbox toward cancer immunotherapy
- (4)
  What the future holds.
The impact of SST2 trafficking and signaling in the treatment of pancreatic neuroendocrine tumors
2021, Molecular and Cellular Endocrinology
Pancreatic neuroendocrine tumors (Pan-NETs), are heterogeneous neoplasms, whose incidence and prevalence are increasing worldwide. Pan-NETs are characterized by the expression of somatostatin receptors (SSTs). In particular, SST2 is the most widely distributed SST in NETs, thus representing the main molecular target for somatostatin analogs (SSAs). SSAs are currently approved for the treatment of well-differentiated NETs, and radionuclide-labeled SSAs are used for diagnostic and treatment purposes. SSAs, by binding to SSTs, have been shown to inhibit hormone secretion and thus provide control of hypersecretion symptoms, when present, and inhibit tumor proliferation. After SSA binding to SST2, the fate of the receptor is determined by trafficking mechanisms, crucial for the response to endogenous or pharmacological ligands. Although SST2 acts mostly through G protein-dependent mechanism, receptor-ligand complex endocytosis and receptor trafficking further regulate its function.
SST2 mediates the decrease of hormone secretion via a G protein-dependent mechanism, culminating with the inhibition of adenylyl cyclase and calcium channels; it also inhibits cell proliferation and increases apoptosis through the modulation of protein tyrosine phosphatases. Moreover, SST2 inhibits angiogenesis and cell migration. In this respect, the cross-talk between SST2 and its interacting proteins, including Filamin A (FLNA) and aryl hydrocarbon receptor-interacting protein (AIP), plays a crucial role for SST2 signaling and responsiveness to SSAs.
This review will focus on recent studies from our and other groups that have investigated the trafficking and signaling of SST2 in Pan-NETs, in order to provide insights into the mechanisms underlying tumor responsiveness to pharmacological treatments.
Metallic radionuclides for diagnostic imaging and cancer radiotherapy: The development of theragnostic matched pairs and targeted alpha therapy
2021, Advances in Inorganic Chemistry
This account highlights the development of theragnostic pairs of radionuclides for imaging and therapy. The current use of diagnostic positron emission tomographic imaging with agents radiolabeled with gallium-68 to guide radionuclide therapy with lutetium-177 based agents, is introduced before discussing recent advances that use the positron emitting radionuclide copper-64 for diagnostic imaging and β-emitting radionuclide copper-67 for therapy. The use of cage amine sarcophagine ligands, that have complexes of excellent thermodynamic and kinetic stability with radionuclides of copper(II), to develop new theragnostic radiopharmaceuticals to enable targeting of prostate cancers and a variety of somatostatin positive neuroendocrine tumors, is discussed. The use of in vivo pretargeted radioimmunotherapy utilizing tetrazine trans-cyclooctene click chemistry is discussed focusing on the development of a single radioligand that is able to incorporate both diagnostic and therapeutic radionuclides. Finally, the latest advances in targeted radionuclide therapy with the α-emitting actinium-225 radionuclide are discussed.
The emerging role of cell surface receptor and protein binding radiopharmaceuticals in cancer diagnostics and therapy
2021, Nuclear Medicine and Biology
Targeting specific cell membrane markers for both diagnostic imaging and radionuclide therapy is a rapidly evolving field in cancer research. Some of these applications have now found a role in routine clinical practice and have been shown to have a significant impact on patient management. Several molecular targets are being investigated in ongoing clinical trials and show promise for future implementation. Advancements in molecular biology have facilitated the identification of new cancer-specific targets for radiopharmaceutical development.
Structural modifications of amino acid sequences of radiolabeled peptides for targeted tumor imaging
2020, Bioorganic Chemistry
Molecular imaging techniques are increasingly being used in localization, staging and therapy control of cancer. Due to their unique target specificity for the endogenous receptors, radiopeptides have been used widely for the development of radiopharmaceuticals for targeted tumor imaging in nuclear oncology. It is necessary to modify radiolabeled peptides in order to achieve more effective agents. Structural modifications of amino acid chains have significant effect on the metabolic stability, biological activity and efficiency of peptide conjugates that are currently applied as imaging tracers. There are several ways to modify the peptide chain but the most common strategies include amino acid substitutions, cyclization and multimerization. In this review, we have focused on studies involving these kind of modifications on amino acid sequences of radiolabeled peptides and we have provided an overview of the effects of these chemical modifications on the in vitro and in vivo properties of these radioconjugates and their potential as SPECT (Single photon emission computed tomography) and PET (positron emission tomography) imaging agents.

View all citing articles on Scopus

View full text

[111In-DTPA-D-Phe1]-octreotide, a potential radiopharmaceutical for imaging of somatostatin receptor-positive tumors: synthesis, radiolabeling and in vitro validation

Abstract

Bailliére's Clinical Endocrinology and Metabolism

Lancet

Life Sci

Life Sci

Life Sci

Life Sci

J Clin Endocrinol Metab

[¹¹¹In-DTPA-D-Phe¹]-octreotide, a potential radiopharmaceutical for imaging of somatostatin receptor-positive tumors: synthesis, radiolabeling and in vitro validation