Molecular imaging and therapy of somatostatin receptor positive tumors

Ivanidze, Jana; Roytman, Michelle; Sasson, Arielle; Skafida, Myrto; Fahey, Thomas J.; Osborne, Joseph R.; Dutruel, Silvina P.

doi:10.1016/j.clinimag.2019.04.006

Cited by 34 publications

(32 citation statements)

References 57 publications

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“…Currently, 177 Lu-DOTATATE is gaining breathtaking attention in therapy of NETs followed by 68 Ga-DOTATATE mediated PET imaging for initial diagnosis, and selection of patients for PRRT. 23 The agent is under different clinical trials to get approval from respective authorities in different regions of world. [24][25][26] In Pakistan, we have also developed the freeze-dried kit of DOTATATE for imaging and therapy of NETs at affordable cost.…”

Section: Discussionmentioning

confidence: 99%

¹⁷⁷Lu-DOTATATE Peptide Receptor Radionuclide Therapy: Indigenously Developed Freeze Dried Cold Kit and Biological Response in In-Vitro and In-Vivo Models

2021

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Somatostatin receptors (SStR) based 177Lu-DOTATATE therapy is known as one of the highly effective neuroendocrine tumors (NETs) treatment strategy. Development of DOTATATE freeze-dried kit for imaging and therapy of SStR positive NETs is a prime goal in neuroendocrine cancer research. The present work describes the development of 177Lu-DOTATATE freeze dried cold kit for indigenous needs, through technology development fund (TDF) program offered by Higher Education Commission (HEC) Pakistan. The parameters for freeze dried kit production was optimized and tested the stored lyophilized cold kits for different time intervals after labeling with 177Lu radioisotope. The effect of ligand to radionuclide ratio, pH and reaction time at 90°C was recorded. Five times greater molar concentration of ligand, pH 5 and 30 min reaction time were the effective reaction conditions for maximum radiochemical yield. The radiolabeling yield at 1 day, 1-week and 4-week post storing period showed ∼100% radiochemical yield. The biodistribution study using rat model depicted the absence of non-targeted accumulation while glomerular filtration rate also explains the rapid renal washout. Cytotoxicity study showed quite favorable results for subjecting the radiopharmaceutical to clinical practice in Pakistan.

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Section: Discussionmentioning

confidence: 99%

¹⁷⁷Lu-DOTATATE Peptide Receptor Radionuclide Therapy: Indigenously Developed Freeze Dried Cold Kit and Biological Response in In-Vitro and In-Vivo Models

2021

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“…The results of 68 Ga-SSTR-PET analysis as predictor factor seem even more important than the tumor site or the type of tracer [54]. PET imaging based on SSTRs overexpression at the level of NETs (traditionally at gastro-entero-pancreatic site) is mostly targeted to SSTR2 [55]. 68 Ga-Dotatate-PET offers the advantages of a relatively low radiation dose in association to the possibility of results quantification and it seems superior to 111 Indium ( 111 In)-Pentetreotide according to some studies [55].…”

Section: Integrating the Immunochemistry Profile In Daily Routine Pramentioning

confidence: 99%

“…PET imaging based on SSTRs overexpression at the level of NETs (traditionally at gastro-entero-pancreatic site) is mostly targeted to SSTR2 [55]. 68 Ga-Dotatate-PET offers the advantages of a relatively low radiation dose in association to the possibility of results quantification and it seems superior to 111 Indium ( 111 In)-Pentetreotide according to some studies [55]. However, the use of SSTR imaging techniques is not adequate for a pituitary somatotropinoma in daily practice.…”

Section: Integrating the Immunochemistry Profile In Daily Routine Pramentioning

confidence: 99%

Somatostatin receptors in normal and acromegalic somatotroph cells: the U-turn of the clinician to immunohistochemistry report – a review

Ionovici

Cârșote

Terzea

et al. 2020

Rom J Morphol Embryol

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This is a narrative review of literature introducing somatostatin receptors (SSTRs) as part of understanding the somatotroph cells since they are positive in normal cells but also in tumoral cells as seen in somatotropinoma, a growth hormone (GH)-producing neoplasia, which causes acromegaly. They are five subtypes of SSTRs (1 to 5), which are immunohistochemically positive in different proportions in somatotropinomas. SSTR types 2 and 5 are most frequent in GH-secreting adenomas and they are both targeted by medical therapy with somatostatin analogues (SSTAs) like first generation Octreotide and Lanreotide (mainly targeting SSTR2) and second generation Pasireotide (with highest affinity for SSTR5), thus heterogeneous SSTRs configuration into the tumor explains different pattern of response to treatment and it might predict it once the SSTRs immunostaining is performed. Monoclonal antibodies are used for immunohistochemical detection of SSTRs; currently, a lack of standardization is presented, and scoring systems, such as Volante, H-score or human epidermal growth factor receptor 2 (HER2)score, are applied. Immunoreactive markers like SSTRs are the U-turn in clinical practice regarding somatotropinomas since the configuration of subtypes 2 and 5 explains the responsiveness to medical therapy like SSTA. Further achievement of disease control is imperiously necessary because acromegaly has an increased rate of morbidity and mortality.

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“…Treatment options include surgical resection, for localized disease, and systemic treatments such as chemotherapy, peptide receptor radionuclide therapy (PRRT) and somatostatin analogues for metastatic disease [4-8]. In all cases, however, molecular imaging is heavily utilized for treatment selection and guidance [9-11]. Image-guided therapy in NETs is especially important given the drastic variability in phenotype and functionality of NET subtypes.…”

Section: Introductionmentioning

confidence: 99%

A side-by-side evaluation of [18F]FDOPA enantiomers for non-invasive detection of neuroendocrine tumors by positron emission tomography

Narayan

Lisok

et al. 2019

Oncotarget

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Neuroendocrine tumors (NETs) are an extremely heterogenous group of malignancies with variable clinical behavior. Molecular imaging of patients with NETs allows for effective patient stratification and treatment guidance and is crucial in selection of targeted therapies. Positron emission tomography (PET) with the radiotracer L-[18F]FDOPA is progressively being utilized for non-invasive in vivo visualization of NETs and pancreatic β-cell hyperplasia. While L-[18F]FDOPA-PET is a valuable tool for disease detection and management, it also exhibits significant diagnostic limitations owing to its inherent physiological uptake in off-target tissues. We hypothesized that the D-amino acid structural isomer of that clinical tracer, D-[18F]FDOPA, may exhibit superior clearance capabilities owing to a reduced in vivo enzymatic recognition and enzyme-mediated metabolism. Here, we report a side-by-side evaluation of D-[18F]FDOPA with its counterpart clinical tracer, L-[18F]FDOPA, for the non-invasive in vivo detection of NETs. In vitro evaluation in five NET cell lines, including invasive small intestinal neuroendocrine carcinomas (STC-1), insulinomas (TGP52 and TGP61), colorectal adenocarcinomas (COLO-320) and pheochromocytomas (PC12), generally indicated higher overall uptake levels of L-[18F]FDOPA, compared to D-[18F]FDOPA. While in vivo PET imaging and ex vivo biodistribution studies in PC12, STC-1 and COLO-320 mouse xenografts further supported our in vitro data, they also illustrated lower off-target retention and enhanced clearance of D-[18F]FDOPA from healthy tissues. Cumulatively our results indicate the potential diagnostic applications of D-[18F]FDOPA for malignancies where the utility of L-[18F]FDOPA-PET is limited by the physiological uptake of L-[18F]FDOPA, and suggest D-[18F]FDOPA as a viable PET imaging tracer for NETs.

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Molecular imaging and therapy of somatostatin receptor positive tumors

Cited by 34 publications

References 57 publications

¹⁷⁷Lu-DOTATATE Peptide Receptor Radionuclide Therapy: Indigenously Developed Freeze Dried Cold Kit and Biological Response in In-Vitro and In-Vivo Models

¹⁷⁷Lu-DOTATATE Peptide Receptor Radionuclide Therapy: Indigenously Developed Freeze Dried Cold Kit and Biological Response in In-Vitro and In-Vivo Models

Somatostatin receptors in normal and acromegalic somatotroph cells: the U-turn of the clinician to immunohistochemistry report – a review

A side-by-side evaluation of [18F]FDOPA enantiomers for non-invasive detection of neuroendocrine tumors by positron emission tomography

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Molecular imaging and therapy of somatostatin receptor positive tumors

Cited by 34 publications

References 57 publications

177Lu-DOTATATE Peptide Receptor Radionuclide Therapy: Indigenously Developed Freeze Dried Cold Kit and Biological Response in In-Vitro and In-Vivo Models

177Lu-DOTATATE Peptide Receptor Radionuclide Therapy: Indigenously Developed Freeze Dried Cold Kit and Biological Response in In-Vitro and In-Vivo Models

Somatostatin receptors in normal and acromegalic somatotroph cells: the U-turn of the clinician to immunohistochemistry report – a review

A side-by-side evaluation of [18F]FDOPA enantiomers for non-invasive detection of neuroendocrine tumors by positron emission tomography

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¹⁷⁷Lu-DOTATATE Peptide Receptor Radionuclide Therapy: Indigenously Developed Freeze Dried Cold Kit and Biological Response in In-Vitro and In-Vivo Models

¹⁷⁷Lu-DOTATATE Peptide Receptor Radionuclide Therapy: Indigenously Developed Freeze Dried Cold Kit and Biological Response in In-Vitro and In-Vivo Models