Peptide Receptor Radionuclide Therapy and Primary Brain Tumors: An Overview

Abstract

Primary brain tumors (PBTs) are some of the most difficult types of cancer to treat, and despite advancements in surgery, chemotherapy and radiotherapy, new strategies for the treatment of PBTs are needed, especially for those with poor prognosis such as inoperable/difficult-to-reach lesions or relapsing disease. In regard to the last point, malignant primary brain tumors remain some of the most lethal types of cancer. Nuclear medicine may provide exciting new weapons and significant contributions in the treatment of PBTs. In this review, we performed literature research in order to highlight the possible role of peptide receptor radionuclide therapy (PRRT) in the treatment of PBTs with radiolabeled molecules that bind with high-affinity transmembrane receptors such as somatostatin receptors (SSTRs), neurokinin type-1 receptor and prostate-specific membrane antigen (PSMA). These receptors are overexpressed in some cancer types such as gliomas, meningiomas, pituitary tumors and medulloblastomas. A comprehensive overview of possible applications in this field will be shown, providing knowledge about benefits, feasibility, developments and limitations of PRRT in this type of tumor, also revealing new advantages in the management of the disease.

A Historical Review of Brain Drug Delivery

“…No imaging of the tumor was possible following the IV injection of the [ 111 In-DTPA, PEG 3400 -biotinyl]-EGF not bound to the OX26 TfRMAb [804]. Recent reviews have discussed the use of peptide radiopharmaceuticals for either therapeutic [807] or diagnostic [808] agents for brain disease. Peptides have the potential for many medical applications in the CNS as there are >100 peptide systems in the brain [801,809].…”

Peptides for trans‐blood–brain barrier delivery

“…The most popular radiolabelled somatostatin analogues for therapeutic purposes in clinical practice are 90 Y-DOTATOC and 177 Lu-DOTATATE. 30 In addition to prolific use outside the CNS, somatostatin radiopharmaceuticals are effective theranostic agents in the CNS. [32][33][34] Analogues of the naturally occurring, 11 amino acid neuropeptide, substance P, constitute another class of theranostic agents with intrinsic CNS-targeting properties.…”

The Impact of PET/CT on Paediatric Oncology

“…68 Gallium is obtained from a generator and is therefore readily available in centres with the 68 Germanium/ 68 Gallium generator; in contrast, [ 123 I]mIBG is cyclotron-produced, which hampers availability in centres far from a cyclotron. Finally the special resolution with PET tracers is better than that of [ 123 I]mIBG, Figure 2 [31]. There is growing interest in the use of PRRT in these patients [32,33].…”

“…Somatostatin receptors specifically somatostatin receptor subtype 2 (SSTR2) is overexpressed in paediatric tumours, including medulloblastoma and primitive neuroectodermal tumours (PNET). If a brain tumour is ([ 68 Ga]DOTA-SSA-avid, this opens up the possibility of PRRT with either [ 177 Lu]DOTATATE or [ 90 Y]DOTANOC [31].…”

“…On the transaxial images illustrates extensive abnormal uptake in the expansile skull lesions. If a tumour is ([ 68 Ga]DOTA-SSA-avid, this opens up the possibility of PRRT with either [ 177 Lu]DOTATATE or [ 90 Y]DOTANOC[31]. There is growing interest in the use of PRRT in these patients[32,33].…”