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Receptor targeting for tumor localisation and therapy with radiopeptides
A Heppeler1, S Froidevaux, A N Eberle
1Laboratory of Endocrinology, Department of Research, University Hospital and University Childrenn's Hospital, Basel, Switzerland.
Abstract:
Receptor targeting with radiolabeled peptides has become very important in nuclear oncology in the past few years. The most frequently used peptides in the clinic are analogs of somatostatin (SRIF), e.g. OctreoScan, which contain chelators for the radioisotopes 111In, 86Y, 90Y, 67Ga, 68Ga and 64Cu or for 99mTc and 188Re. and were labelled with the halogens 123I and 18F. Radiolabeled analogs of &alpha-melanocyte-stimulating hormone (&alpha-MSH), neurotensin, vasoactive intestinal peptide (VIP), bombesin (BN), substance P (SP) and gastrin/cholecystokinin (CCK) are also being developed, evaluated in vitro and in vivo and tested for clinical application. This review focuses on the expression in tumors and the regulation of receptors for these neuropeptides as well as the development of novel chelator-peptide conjugates suitable for in vivo scintigraphy or internal radiotherapy. The state of the art of radiopeptide pharmaceuticals is illustrated with four SRIF analogs, modified with the macrocyclic chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA): [D-Phe1]-octreotide (DOTAOC), [D-Phe1, Tyr3]-octreotide (DOTATOC), vapreotide (DOTAVAP) and lanreotide (DOTALAN). DOTA is almost a universal chelator capable of strongly encapsulating hard metals such as 111In and 67Ga for Single Photon Emission Tomography (SPET), 68Ga, 86Y and 64Cu for Positron Emission Tomography (PET) as well as 90Y for receptor-mediated radionuclide therapy and radiolanthanides which exhibit different interesting decay schemes. From biodistribution studies in experimental animals and from clinical data it is concluded that DOTATOC is currently the most suitable SRIF radiopeptide with the best potential in the clinic.
Insights
Radiolabeled peptides, particularly somatostatin analogs like DOTATOC, are crucial in nuclear oncology for tumor imaging and therapy. DOTATOC shows the most promise for clinical applications due to its effectiveness in targeting somatostatin receptors.
Area of Science:
- Nuclear oncology
- Radiopharmaceutical chemistry
- Molecular imaging
Background:
- Receptor targeting with radiolabeled peptides is a rapidly advancing field in nuclear oncology.
- Somatostatin analogs (SRIF) are widely used, with various radioisotopes and chelators enabling diagnostic and therapeutic applications.
- Development of other radiolabeled neuropeptide analogs is ongoing for diverse clinical uses.
Purpose of the Study:
- To review the expression and regulation of neuropeptide receptors in tumors.
- To discuss the development of novel chelator-peptide conjugates for nuclear oncology.
- To highlight the clinical potential of somatostatin receptor-targeted radiopeptides.
Main Methods:
- Focus on the development and evaluation of novel chelator-peptide conjugates.
- Utilized macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for modifying SRIF analogs.
- Examined four DOTA-modified SRIF analogs: DOTAOC, DOTATOC, DOTAVAP, and DOTALAN.
Main Results:
- DOTA is a versatile chelator for various radioisotopes used in SPECT, PET, and radionuclide therapy.
- Biodistribution studies in animals and clinical data were analyzed.
- DOTATOC emerged as the most suitable SRIF radiopeptide with significant clinical potential.
Conclusions:
- DOTATOC demonstrates superior performance among evaluated SRIF radiopeptides.
- The development of DOTA-conjugated radiopeptides offers promising avenues for cancer diagnosis and therapy.
- Continued research into receptor targeting with radiolabeled peptides is vital for advancing nuclear oncology.