Radiolabeled regulatory peptides for imaging and therapy

Abstract

Purpose of review The purpose of the present review is to describe new, innovative strategies of diagnosing and treating specific human cancers using a cadre of radiolabeled regulatory peptides. Recent findings Peptide receptor-targeted radionuclide therapy is a method of site-directed radiotherapy that specifically targets human cancers expressing a cognate receptor-subtype in very high numbers. Ideally, the procedure targets only the primary or metastatic disease and is minimally invasive, with little radiation damage to normal, collateral tissues. For treatment strategies of this type to be effective, it is critical to evaluate the toxicity of the treatment protocol, the radiation dosimetry of the therapeutic regimen, and the biological profile of the radiopharmaceutical, including biodistribution and pharmacokinetics of the drug. Site-directed molecular imaging procedures via γ-scintigraphy can address many of the critical issues associated with peptide receptor-targeted radionuclide therapy and it is, therefore, necessary to describe the effective balance between the clinical benefits and risks of this treatment strategy. Summary Continued development in the design or chemical structure of radiolabeled, biologically active peptides could do much to improve the targeting ability of these drugs, thereby creating new and innovative strategies for diagnosis or treatment of human cancers.

Preclinical evaluation of gastrin derivatives labelled with ¹¹¹In: Radiolabelling, affinity profile and pharmacokinetics in rats

“…This approach is of particular interest for application in oncology because human cancer cells overexpress many peptide receptors as molecular targets 1,2 . As cholecystokinin receptor subtype 2 (CCK-2) is overexpressed in a high percentage in a large number of neuroendocrine tumours, in particular medullary thyroid carcinoma, small cell lung cancer, astrocytomas, and neuroendocrine gut tumours, CCK-2 receptor which also has high affinity for gastrin, might be a suitable target for radionuclide imaging and therapy [3][4][5][6] .…”

Expression, purification, refolding, and characterization of octreotide-interleukin-2: A chimeric tumor-targeting protein

“…These therapies result in less side effects and a better quality of life for the patients (1). The selective delivery of bioactive agents (e.g., cytotoxic drugs, radionuclides, or immunostimulatory cytokines) to the tumor site represents one of the most promising strategies, which has unprecedented efficacy and tolerability, in the development of diagnostic and anticancer therapies (2)(3)(4). Using the strong antineoplastic activities of peptide-guided tumor-targeting cytokines and tumor-targeting immunocytokines in preclinical models of solid cancers as an example (5-9), we constructed a peptide-guided interleukin-2 (IL-2) chimeric protein that could particularly enrich tumor sites with immunocytokines.…”

“…SST is secreted from a broad range of tissues, including pancreas, the intestinal tract, and regions of the central nervous system outside of the hypothalamus (15). SST acts by binding to a family of five SST receptors (SSTR [1][2][3][4][5], all of which are G protein-coupled receptors (16). Subsequently, SSTRs were found to secrete from a wide range of tissues, including lymphoid cells, diabetic islets, and the nervous and gastro-entero-pancreatic systems (17)(18)(19).…”

Marcadores moleculares derivados da Bombesina para diagnóstico de tumores por SPECT e PET

“…TABELA 37 -Índices hematimétricos dos animais controles e tratados 24 horas, 7 e 14 dias após a administração de solução de NaCl 0,9 % p/v ou dos derivados YG 5 -DTPA e YG 5 N-DTPA (n = 5). Dados: VCM -volume corpuscular médio; HCM -hemoglobina corpuscular média; CHCM -concentração de hemoglobina corpuscular média.…”

“…The BBN derivative YG 5 N conjugated to DTPA or DOTA is a promising and safe tool for BB 2 expressing tumour diagnosis by SPECT and PET. 5 …”