DOTATOC: A powerful new tool for receptor-mediated radionuclide therapy

This study presents the first successful use of a peptidic vector, DOTATOC, labelled with the β-emitting radioisotope yttrium-90, for the treatment of a patient with somatostatin receptor-positive abdominal metastases of a neuroendocrine carcinoma of unknown localization. Tumour response and symptomatic relief were achieved. In addition, the new substance DOTA-TOC was labelled with the diagnostic chemical analogue indium-111 and studied in three patients with histopathologically verified neuroendocrine abdominal tumours for its diagnostic sensitivity and compared with the commercially available OctreoScan. In all patients the kidney-to-tumour uptake ratio (in counts per pixel) was on average 1.9-fold lower with111In-DOTATOC than with OctreoScan. DOTATOC could be a potential new diagnostic and therapeutic agent in the management of neuroendocrine tumour

A decision-making framework for the implementation of remanufacturing in rechargeable energy storage system in hybrid and electric vehicles

As data from manufacturing and digital intelligence become a pervasive feature of our economy, it becomes increasingly important to leverage on this data in the creation of new forms of value. Within emerging concepts such as Industry 4.0 (I4.0) and the Internet of Things (IoT), understanding decision-making and stakeholders’ interaction is important in optimising manufacturing and post-manufacturing processes. Of interest is the post-manufacturing phase for the Rechargeable Energy Storage system, (RESS), a battery system embedded in hybrid and electric automobiles. This research develops a decision-making framework for the RESS component, employing data-driven remanufacturing as the circular approach for implementation. Findings highlight useful manufacturing data employed in remanufacturing for the RESS technology. This study concludes by giving recommendations on how decisions made by stakeholders and their interaction can inform manufacturers on design for remanufacturing

Metal ion-dependent biological properties of a chelator-derivatised somatostatin analogue for tumour targeting

A publicar na Revista Chemistry a European JournalSomatostatin-based radioligands were shown to have sensitive imaging properties for neuroendocrine tumours and their metastases. The potential of [55Co]DOTATOC (DOTATOC = 4,7, 10-tricarboxymethyl-1,4,7,10- tetraazacyclododecane-1-yl-acetyl-DPhe- Lys-Tyr-D-Trp-Lys-Thr-Lys-1- threoninol (disulfide bond) as a new radiopharmaceutical agent for PET was evaluated. 57Co was used as a surrogate of the positron emitter 55Co and the pharmacokinetics of [57Co]DOTATOC was investigated using two nude mouse models. The somatostatin receptor subtype (sst1-5) affinity profile of [natCo]DOTA-TOC was assessed using autoradiographic methods on membranes transfected with human somatostatin receptor subtypes. These studies revealed that [57Co]DOTATOC is an sst2-specific radiopeptide presenting the highest affinity ever found for the sst2 receptor subtype. The rate of internalisation into the AR4-2J cell line also was the highest found for any somatostatin-based radiopeptide. Biodistribution studies, performed in nude mice bearing the AR4-2J tumour or a transfected HEK-sst2 cell-based tumour, showed high and specific uptake in the tumour and in other sst receptor-expressing tissues reflecting the high receptor binding affinity and the high rate of internalisation. The pharmacologic differences between [57Co]DOTATOC and [67Ga]DOTATOC were discussed in terms of the structural parameters found for the chelate models CoII(DOTA)2- and GaIII(DOTA)-, whose X-ray structures were determined. Both chelates show sixfold coordination in pseudooctahedral arrangements

Peptide receptor radiotherapy: a new option for the management of aggressive fibromatosis on behalf of the Italian Sarcoma Group

The management of aggressive fibromatosis (AF) is problematic, and few options are available to patients unsuitable for surgery and resistant to external-beam radiation therapy (EBRT). We report on two patients with fast-growing recurrences of AF resistant to EBRT who obtained protracted clinical benefits with 90Y-DOTATOC. 90Y-DOTATOC should be further investigated in this setting

PET imaging of αvβ3 integrin expression in tumours with 68Ga-labelled mono-, di- and tetrameric RGD peptides

Contains fulltext : 97195.pdf (publisher's version ) (Closed access)PURPOSE: Due to the restricted expression of alpha(v)beta(3) in tumours, alpha(v)beta(3) is considered a suitable receptor for tumour targeting. In this study the alpha(v)beta(3)-binding characteristics of (68)Ga-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared with their (111)In-labelled counterparts. METHODS: A monomeric (E-c(RGDfK)), a dimeric (E-[c(RGDfK)](2)) and a tetrameric (E{E[c(RGDfK)](2)}(2)) RGD peptide were synthesised, conjugated with DOTA and radiolabelled with (68)Ga. In vitro alpha(v)beta(3)-binding characteristics were determined in a competitive binding assay. In vivo alpha(v)beta(3)-targeting characteristics of the compounds were assessed in mice with subcutaneously growing SK-RC-52 xenografts. In addition, microPET images were acquired using a microPET/CT scanner. RESULTS: The IC(50) values for the Ga(III)-labelled DOTA-E-c(RGDfK), DOTA-E-[c(RGDfK)](2) and DOTA-E{E[c(RGDfK)](2)}(2) were 23.9 +/- 1.22, 8.99 +/- 1.20 and 1.74 +/- 1.18 nM, respectively, and were similar to those of the In(III)-labelled mono-, di- and tetrameric RGD peptides (26.6 +/- 1.15, 3.34 +/- 1.16 and 1.80 +/- 1.37 nM, respectively). At 2 h post-injection, tumour uptake of the (68)Ga-labelled mono-, di- and tetrameric RGD peptides (3.30 +/- 0.30, 5.24 +/- 0.27 and 7.11 +/- 0.67%ID/g, respectively) was comparable to that of their (111)In-labelled counterparts (2.70 +/- 0.29, 5.61 +/- 0.85 and 7.32 +/- 2.45%ID/g, respectively). PET scans were in line with the biodistribution data. On all PET scans, the tumour could be clearly visualised. CONCLUSION: The integrin affinity and the tumour uptake followed the order of DOTA-tetramer > DOTA-dimer > DOTA-monomer. The (68)Ga-labelled tetrameric RGD peptide has excellent characteristics for imaging of alpha(v)beta(3) expression with PET

Somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine tumours, current aspects and new perspectives

Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are rare tumours that present many clinical features