Study of the most important physiologic parameter using GSA with sobol method and a PBPK model for individualization of peptide-receptor radionuclide therapy

Background: The incidence of pancreatic Neuroendocrine Tumours (pNETs) has increased considerably in the last few decades. The characteristic features of this tumour and the development of new investigative and therapeutic methods had a great impact on its management. Objective: The aim of this review is to investigate the outcome of Peptide Receptor Radionuclide Therapy (PRRT) in the treatment of pancreatic neuroendocrine tumours. Methods: A comprehensive literature search strategy was used based on two databases (SCOPUS, and PubMed). We considered all studies published in English, evaluating the use of PRRT (177Luteciuim- DOTA-conjugated peptides and 90Yetrium- DOTA- conjugated peptides) in the treatment of pancreatic neuroendocrine tumours as a standalone entity or as a subgroup within the wider category of Gastroenteropancreatic Neuroendocrine Tumours (GEP NETs). Results: PRRT was found to be an effective treatment modality as a monotherapy or in combination with other therapies in the treatment of non-operable and metastatic pNETs where other options are limited. Complete response was reported to be between 2-6% while partial response was achieved in up to 60% of cases. Survival analysis was also impressive. Progression Free Survival (PFS) reached a mean of 34 months and Overall Survival (OS) of 53 months. PRRT also proved to improve patients’ Quality of Life (QoL). Acute and sub-acute side effects like nephrotoxicity and haematotoxicity are usually mild and reversible. Conclusion: PRRT is well tolerated and effective treatment option for non-operable and/or metastatic pNETs. Side effects are usually mild and reversible. Larger randomized controlled trails need to be done to compare PRRT with other treatment modalities and to provide more detailed guidelines regarding patient selections, the choice of PRRT, follow up and response assessment to maximum potential benefit.

Download Full-text

Molecular imaging & peptide receptor radionuclide therapy

Advances in Pulmonary Neuroendocrine Tumor Management ◽

10.2217/ebo.12.80 ◽

2013 ◽

pp. 20-34

Author(s):

Richard P Baum ◽

Harshad R Kulkarni ◽

Dieter Hörsch

Keyword(s):

Molecular Imaging ◽

Radionuclide Therapy ◽

Peptide Receptor Radionuclide Therapy ◽

Peptide Receptor

Download Full-text

Molecular profiling of neuroendocrine tumours to predict response and toxicity to peptide receptor radionuclide therapy

The Lancet Oncology ◽

10.1016/s1470-2045(20)30323-5 ◽

2020 ◽

Vol 21 (9) ◽

pp. e431-e443 ◽

Cited By ~ 1

Author(s):

Lisa Bodei ◽

Heiko Schöder ◽

Richard P Baum ◽

Ken Herrmann ◽

Jonathan Strosberg ◽

...

Keyword(s):

Radionuclide Therapy ◽

Neuroendocrine Tumours ◽

Peptide Receptor Radionuclide Therapy ◽

Molecular Profiling ◽

Peptide Receptor

Download Full-text

Intraindividual comparison of [177Lu]Lu-DOTA-EB-TATE and [177Lu]Lu-DOTA-TOC

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-020-05177-z ◽

2021 ◽

Author(s):

Heribert Hänscheid ◽

Philipp E. Hartrampf ◽

Andreas Schirbel ◽

Andreas K. Buck ◽

Constantin Lapa

Keyword(s):

Radionuclide Therapy ◽

Therapeutic Agent ◽

Somatostatin Receptor ◽

Absorbed Dose ◽

Peptide Receptor Radionuclide Therapy ◽

Somatostatin Analogue ◽

Target Tissue ◽

Peptide Receptor ◽

Intraindividual Comparison ◽

Administered Activity

Abstract Purpose The radiolabelled somatostatin analogue [177Lu]Lu-DOTA-EB-TATE binds to albumin via Evans blue, thereby increasing the residence time in the blood and potentially allowing more therapeutic agent to be absorbed into the target tissue during peptide receptor radionuclide therapy. It was tested in selected patients whether the substance is superior to [177Lu]Lu-DOTA-TOC. Methods Activity kinetics in organs and tumours after [177Lu]Lu-DOTA-EB-TATE and [177Lu]Lu-DOTA-TOC were compared intraindividually in five patients with progressive somatostatin receptor-positive disease scheduled for radionuclide therapy. Results In comparison to [177Lu]Lu-DOTA-TOC, tumour doses per administered activity were higher for [177Lu]Lu-DOTA-EB-TATE in 4 of 5 patients (median ratio: 1.7; range: 0.9 to 3.9), kidney doses (median ratio: 3.2; range: 1.6 to 9.8) as well as spleen doses (median ratio: 4.7; range 1.2 to 6.2) in all patients, and liver doses in 3 of 4 evaluable patients (median ratio: 4.0; range: 0.7 to 4.9). The tumour to critical organs absorbed dose ratios were higher after [177Lu]Lu-DOTA-TOC in 4 of 5 patients. Conclusions Prior to a treatment with [177Lu]Lu-DOTA-EB-TATE, it should be assessed individually whether the compound is superior to established substances.

Download Full-text