The Current Status and Future Potential of Theranostics to Diagnose and Treat Childhood Cancer

Abstract

In theranostics (i.e., therapy and diagnostics) radiopharmaceuticals are used for both therapeutic and diagnostic purposes by targeting one specific tumor receptor. Biologically relevant compounds, e.g., receptor ligands or drugs, are labeled with radionuclides to form radiopharmaceuticals. The possible applications are multifold: visualization of biological processes or tumor biology in vivo, diagnosis and tumor staging, therapy planning, and treatment of specific tumors. Theranostics research is multidisciplinary and allows for the rapid translation of potential tumor targets from preclinical research to "firstin-man" clinical studies. In the last decade, the use of theranostics has seen an unprecedented value for adult cancer patients. Several radiopharmaceuticals are routinely used in clinical practice (e.g., [ 68 Ga/ 177 Lu]DOTATATE), and dozens are under (pre)clinical development. In contrast to these successes in adult oncology, theranostics have scarcely been developed to diagnose and treat pediatric cancers. To date, [ 123/131 I] meta-iodobenzylguanidine ([ 123/131 I]mIBG) is the only available and approved theranostic in pediatric oncology. mIBG targets the norepinephrine transporter, expressed by neuroblastoma tumors. For most pediatric tumors, including neuroblastoma, there is a clear need for novel and improved radiopharmaceuticals for imaging and therapy. The strategy of theranostics for pediatric oncology can be divided in (1) the improvement of existing theranostics, (2) the translation of theranostics developed in adult oncology for pediatric purposes, and (3) the development of novel theranostics for pediatric tumorspecific targets. Here, we describe the recent advances in theranostics development in pediatric oncology and shed a light on how this methodology can affect diagnosis and provide additional treatment options for these patients.

Bombesin Receptor Family Activation and CNS/Neural Tumors: Review of Evidence Supporting Possible Role for Novel Targeted Therapy

“…Using PCR, GRPR mRNA was found in three human neuroblastoma cell lines (IMR-32, SK-N-SH, LAN-1) (184). Similarly, in binding studies in human neuroblastoma cell lines, in a study using 125 I-GRP combined with GRPR-crosslinking, SK-N-SH neuroblastoma cells were found to possess a GRPR of identical molecular weight as that on Swiss 3T3 fibroblasts (192).…”

“…Therefore, particularly in the case of glioblastomas, there is increased interest in newer approaches in treatment. In other non-CNS tumors (as reviewed earlier) the ectopic expression/ overexpression of various peptide receptors is increasingly being applied and investigated for its possible diagnostic and therapeutic approaches for treatment of these tumors (10,73,124,125,(132)(133)(134)(135)(136). In the case of gliomas and particularly for glioblastomas, the over-/ectopic expression of the BnR family has been investigated in a number of studies and may provide new therapeutic approaches, as recently used in non-CNS tumors (prostate, colon, etc.)…”

“…Tumor imaging is involved in all stages of the management of potentially malignant/malignant CNS/neural tumors (125,(235)(236)(237)(238)(239). Specifically, imaging is required at the initial stages of investigation to assess the location of the primary and extent of the disease, as this will determine the therapeutic approach (surgery, radiation, chemotherapeutic).…”

“…There are also numerous studies of PRRT with radiolabeled BnR analogues in patients with breast cancer (17,23,25,73,269), and other non-endocrine cancer cells (73), which show promise. Third, because of the success of tumor localization and PRRT-mediated cytotoxicity with radiolabeled somatostatin analogues in NETs, as well as limited studies showing promise with PRRT with radiolabeled somatostatin analogues in some patients with symptomatic/malignant CNS/neural tumors (meningiomas) (270)(271)(272)(273), malignant neuroblastomas (274,275), there is increased interest in applying nuclear medicine approaches to other CNS/ neural tumors (125,235,240,276,277).…”

“…A physiological role for the BRS-3 receptor has yet to be completely defined; however, recently studies suggest an important role in metabolic homeostasis, in glucose and insulin regulation, in obesity and diabetes mellitus, in the regulation of body temperature, and in feeding behavior ( 14 , 44 , 68 , 121 – 123 ). For each of the three BnR subtypes, numerous studies support them playing important roles in regulating the growth of normal/neoplastic tissues ( 3 , 9 , 10 , 12 , 14 , 21 , 42 , 102 , 124 , 125 ).…”