PET radiometals for antibody labeling

Abstract

Recent advances in molecular characterization of tumors have made possible the emergence of new types of cancer therapies where traditional cytotoxic drugs and nonspecific chemotherapy can be complemented with targeted molecular therapies. One of the main revolutionary treatments is the use of monoclonal antibodies (mAbs) that selectively target the disseminated tumor cells while sparing normal tissues. mAbs and related therapeutics can be efficiently radiolabeled with a wide range of radionuclides to facilitate preclinical and clinical studies. Non-invasive molecular imaging techniques, such as Positron Emission Tomography (PET), using radiolabeled mAbs provide useful information on the whole-body distribution of the biomolecules, which may enable patient stratification, diagnosis, selection of targeted therapies, evaluation of treatment response, and prediction of dose limiting tissue and adverse effects. In addition, when mAbs are labeled with therapeutic radionuclides, the combination of immunological and radiobiological cytotoxicity may result in enhanced treatment efficacy. The pharmacokinetic profile of antibodies demands the use of long half-life isotopes for longitudinal scrutiny of mAb biodistribution and precludes the use of well-stablished short half-life isotopes. Herein, we review the most promising PET radiometals with chemical and physical characteristics that make the appealing for mAb labeling, highlighting those with theranostic radioisotopes.

Antibody Fragment and Affibody ImmunoPET Imaging Agents: Radiolabelling Strategies and Applications

“…Radiometals with longer half‐lives, such as 64 Cu ( t 1/2 =12.7 h) and 111 In ( t 1/2 =2.8 days), have been used for many years for the labelling and imaging of intact antibodies . The half‐life of 64 Cu also makes it suitable for imaging larger fragments such as minibodies, (Fab′) 2, Fab and diabodies that have slower clearance rates.…”

“…64 Cu, 68 Ga, 89 Zr and 44 Sc Radiometalsw ith longerh alf-lives, such as 64 Cu (t1 = 2 = 12.7 h) and 111 In (t1 = 2 = 2.8 days), have been used form any years for the labellinga nd imagingo fi ntact antibodies. [55] The half-life of 64 Cu also makes it suitable fori maging largerf ragments such as minibodies,( Fab') 2, Fab and diabodies that have slower clearance rates.K ey pioneering studies of antibody fragments for PET imaging have been conducted using 64 Cu. [29,56] 1,4,7,10tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) chelation methods have been the mainstay for 64 Cu labelling of antibody fragments.…”

CD146‐Targeted Multimodal Image‐Guided Photoimmunotherapy of Melanoma

“…Sci. [30] These results demonstrate that 89 Zr-Df-YY146 PET is a very promising imaging technique to delineate CD146-positive melanomas. of the radiotracer.…”

Manganese in PET imaging: Opportunities and challenges

“…However, 52g Mn also offers a suitable t 1/2 for immunoPET applications while displaying a lower β + energy and a higher β + intensity than 89 Zr (Table ). Thus, 52g Mn may represent a promising, alternative radiometal for applications in immunoPET …”