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|Title:||Influence of tumour size on the efficacy of targeted alpha therapy with 213Bi-[DOTA0,Tyr3]-octreotate|
|Authors:||CHAN Ho Sze; KONIJNENBERG M.w.; DE BLOIS Erik; KOELEWIJN S.j.; BAUM Richard; MORGENSTERN Alfred; BRUCHERTSEIFER Frank; BREEMAN Wouter; DE JONG Marion|
|Citation:||EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING vol. 6 no. 6|
|Type:||Articles in periodicals and books|
|Abstract:||Background Targeted alpha therapy has been postulated to have great potential for the treatment of small clusters of tumour cells as well as small metastases. 213Bismuth, an α-emitter with a half-life of 46 min, has shown to be effective in preclinical as well as in clinical applications. In this study, we evaluated whether 213Bi-[DOTA0, Tyr3]-octreotate (213Bi-DOTATATE), a 213Bi-labelled somatostatin analogue with high affinity for somatostatin receptor subtype 2 (SSTR2), is suitable for the treatment of larger neuroendocrine tumours overexpressing SSTR2 in comparison to its effectiveness for smaller tumours. We performed a preclinical targeted radionuclide therapy study with 213Bi-DOTATATE in animals bearing tumours of different sizes (50 and 200 mm3) using two tumour models: H69 (human small cell lung carcinoma) and CA20948 (rat pancreatic tumour). Methods Pharmacokinetics was determined for calculation of dosimetry in organs and tumours. H69- or CA20948-xenografted mice with tumour volumes of approximately 120 mm3 were euthanized at 10, 30, 60 and 120 min post injection of a single dose of 213Bi-DOTATATE (1.5–4.8 MBq). To investigate the therapeutic efficacy of 213Bi-DOTATATE, xenografted H69 and CA20948 tumour-bearing mice with tumour sizes of 50 and 200 mm3 were administered daily with a therapeutic dose of 213Bi-DOTATATE (0.3 nmol, 2–4 MBq) for three consecutive days. The animals were followed for 90 days after treatment. At day 90, mice were injected with 25 MBq 99mTc-DMSA and imaged by SPECT/CT to investigate possible renal dysfunction due to 213Bi-DOTATATE treatment. Results Higher tumour uptakes were found in CA20948 tumour-bearing animals compared to those in H69 tumour-bearing mice with the highest tumour uptake of 19.6 ± 6.6 %IA/g in CA20948 tumour-bearing animals, while for H69 tumour-bearing mice, the highest tumour uptake was found to be 9.8 ± 2.4 %IA/g. Nevertheless, as the anti-tumour effect was more pronounced in H69 tumour-bearing mice, the survival rate was higher. Furthermore, in the small tumour groups, no regrowth of tumour was found in two H69 tumour-bearing mice and in one of the CA20948 tumour-bearing mice. No renal dysfunction was observed in 213Bi-DOTATATE-treated mice after the doses were applied. Conclusions 213Bi-DOTATATE demonstrated a great therapeutic effect in both small and larger tumour lesions. Higher probability for stable disease was found in animals with small tumours. 213Bi-DOTATATE was effective in different neuroendocrine (H69 and CA20948) tumour models with overexpression of SSTR2 in mice.|
|JRC Directorate:||Nuclear Safety and Security|
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