The theranostic promise for Neuroendocrine Tumors in the late 2010s - Where do we stand, where do we go?

Abstract

More than 25 years after the first peptide receptor radionuclide therapy (PRRT), the concept of somatostatin receptor (SSTR)-directed imaging and therapy for neuroendocrine tumors (NET) is seeing rapidly increasing use. To maximize the full potential of its theranostic promise, efforts in recent years have expanded recommendations in current guidelines and included the evaluation of novel theranostic radiotracers for imaging and treatment of NET. Moreover, the introduction of standardized reporting framework systems may harmonize PET reading, address pitfalls in interpreting SSTR-PET/CT scans and guide the treating physician in selecting PRRT candidates. Notably, the concept of PRRT has also been applied beyond oncology, e.g. for treatment of inflammatory conditions like sarcoidosis. Future perspectives may include the efficacy evaluation of PRRT compared to other common treatment options for NET, novel strategies for closer monitoring of potential side effects, the introduction of novel radiotracers with beneficial pharmacodynamic and kinetic properties or the use of supervised machine learning approaches for outcome prediction. This article reviews how the SSTR-directed theranostic concept is currently applied and also reflects on recent developments that hold promise for the future of theranostics in this context.

Pharmacokinetics, radiation dosimetry, acute toxicity and automated synthesis of [18F]AmBF3-TATE

“…The success of radiolabelled somatostatin analogs has been at the forefront of personalized medicine in nuclear medicine [14]. By changing the radioisotope of choice, SSTR2 ligands can be used effectively to diagnose, treat, and monitor response to treatment for NET patients.…”

Peptide receptor radionuclide therapy after NETTER-1 clinical trial: what should not be left behind

“…First of all, it must not be forgotten that PRRT and functional imaging with labeled SSAs have been effectively applied for diagnosis and treatment of several SSTRs-expressing tumors. Beyond current applications, other PRRT potential targets in oncology include meningioma, bronchial NET (small cell lung cancer as well), malignant pheochromocytoma and paraganglioma, medullary thyroid cancer and neuroblastoma [2,3].…”

“…While surgery is frequently curative, this disease is usually chemo-and radio-resistant, thus limited therapeutic options are available in case of metastatic or unresectable tumors, with poor prognosis and no standard approaches. In this scenario, PRRT has shown to achieve good objective response rate and survival, decreasing biomarker levels and improving symptom control [2]. Applications of PRRT in paraganglioma treatment have been assessed in several small cohorts of patients with inoperable disease, with promising outcomes in tumor response and symptoms' control (decreased medication requirements).…”

“…Furthermore, individualizing PRRT, based on lesions' and critical organs' dosimetry on SPECT imaging, usually allows a higher number of 177 Lu-DOTATATE administrations. Keeping an eye on the maximum tolerated dose of the organs at risk, dosimetry ensures to safely maximize the quantity of radiation delivered to target lesions [2]. If properly explored, dosimetry would answer a few open questions about PRRT, i.e., which are the maximum tolerated dose of organs at risk, the threshold for disease response, the number of administrations to safely perform.…”

Ovarian Cancer Targeted Theranostics

“…New targeted strategies are urgently needed to minimize morbidity and mortality associated with ovarian cancer. Theranostic approaches that combine diagnostic imaging with therapy have been shown to improve patient survival in several difficult to treat advanced cancers, and could also be applied to ovarian cancer, a focus of this review (3)(4)(5).…”