Tumor imaging and therapy using radiolabeled somatostatin analogues

Acc Chem Res. 2009 Jul 21;42(7):873-80. doi: 10.1021/ar800188e.

Abstract

Molecular imaging plays an essential role in balancing the clinical benefits and risks of radionuclide-based cancer therapy. To effectively treat individual patients, careful assessment of biodistribution, dosimetry, and toxicity is essential. In this Account, we describe advances that combine features of molecular imaging and radionuclide therapy to provide new avenues toward individualized cancer treatment. Selective receptor-targeting radiopeptides have emerged as an important class of radiopharmaceuticals for molecular imaging and therapy of tumors that overexpress peptide receptors on the cell membrane. After such peptides labeled with gamma-emitting radionuclides bind to their receptors, they allow clinicians to visualize receptor-expressing tumors non-invasively. Peptides labeled with beta-particle emitters could also eradicate receptor-expressing tumors. The somatostatin receptors, which are overexpressed in a majority of neuroendocrine tumors, represent the first and best example of targets for radiopeptide-based imaging and radionuclide therapy. The somatostatin analogue (111)In-octreotide permits the localization and staging of neuroendocrine tumors that express the appropriate somatostatin receptors. Newer modified somatostatin analogues, including Tyr(3)-octreotide and Tyr(3)-octreotate, are successfully being used for tumor imaging and radionuclide therapy. Because there are few effective therapies for patients with inoperable or metastasized neuroendocrine tumors, this therapy is a promising novel treatment option for these patients. Peptide receptor imaging and radionuclide therapy can be combined in a single probe, called a "theranostic". To select patients who are likely to benefit from this type of intervention, we first use a peptide analogue labeled with a diagnostic radionuclide to obtain a scan. Selected patients will be treated using the same or a similar peptide analogue labeled with a therapeutic radionuclide. The development of such theranostics could greatly advance the development of personalized treatments. Apart from patient selection for radionuclide therapy, other imaging applications of targeted radiopeptides include localization of primary tumors, detection of metastatic disease (staging/restaging), dosimetry (prediction of response and radiotoxicity), monitoring effects of surgery, radio(nuclide)therapy or chemotherapy, and detection of progression of disease or relapse (follow up). For further evaluation of tumor receptor expression and to increase the value of cancer targeting using radiopeptides, researchers have introduced and evaluated different radiolabeled analogues of other peptide families, such as cholecystokinin (CCK), gastrin, bombesin, substance P, vasoactive intestinal peptide (VIP), and neuropeptide (NP)-Y analogues. We expect improvements in the development of new peptide analogues: such advances could reduce side effects and allow for the use of combination therapy (for example, combining radiopeptide analogues with chemotherapeutics).

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Humans
  • Neuroendocrine Tumors / diagnostic imaging*
  • Neuroendocrine Tumors / radiotherapy*
  • Octreotide / analogs & derivatives*
  • Octreotide / therapeutic use
  • Pancreatic Neoplasms / diagnostic imaging
  • Pancreatic Neoplasms / radiotherapy
  • Peptides / chemistry
  • Positron-Emission Tomography
  • Radiopharmaceuticals / therapeutic use*
  • Rats
  • Receptors, Somatostatin / metabolism
  • Somatostatin / analogs & derivatives*
  • Somatostatin / therapeutic use
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Peptides
  • Radiopharmaceuticals
  • Receptors, Somatostatin
  • indium-111-octreotide
  • Somatostatin
  • Octreotide