DOTATATE Research Articles

Assessing Krenning's score on 68 Ga-DOTATATE PET-CT and miPSMA score on 68 Ga-PSMA-11 PET-CT in TENIS: a comparison with FDG PET/CT and examining the feasibility of targeted radionuclide therapy.

The objective of this study was to assess receptor expression in metastatic differentiated thyroid carcinoma patients with progressive elevated thyroglobulin and negative iodine scintigraphy, we used 68 Ga-DOTATATE [Gallium-68 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE)] (Krenning's score) and 68 Ga-PSMA-11 (Gallium-68 prostate-specific membrane antigen-11) PET-computed tomography (CT) [molecular imaging prostate-specific membrane antigen (miPSMA) score]. Patients with Krenning's score 3 and above and miPSMA score 2 and above were considered to determine the incidence of patients, who would qualify for treatment with 177 Lu-DOTATATE/PSMA [Lutetium-177 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE)/prostate-specific membrane antigen]-based therapy. In addition, we compared 68 Ga-DOTATATE and 68 Ga-PSMA-11 PET-CT with 2-deoxy-2-[F-18]fluoroglucose ( 18 F-FDG) PET-CT (using maximum standardized uptake value). A total of 74 patients with histopathologically proven metastatic differentiated thyroid carcinoma with thyroglobulin elevation and negative iodine scintigraphy syndrome were studied retrospectively. They all had 18 F-FDG, 68 Ga-DOTATATE, and 68 Ga-PSMA-11 PET-CT scans available for undertaking this analysis. The lesions detected by 68 Ga-DOTATATE and 68 Ga-PSMA-11 were evaluated using Krenning's and miPSMA scores. In addition, quantitative comparisons of maximum standardized uptake values for 68 Ga-DOTATATE and 68 Ga-PSMA-11, as well as with 18 F-FDG, were conducted. Patient-wise analysis revealed positivity rates of 40.5% for 68 Ga-DOTATATE, 41.89% for 68 Ga-PSMA-11, and 75.67% for 18 F-FDG. Among the 74 patients, 14 (18.91%) were deemed eligible for 177 Lu-DOTATATE/PSMA-617 therapy based on Krenning's score of 3 and above both/either miPSMA score of 2 and above on 68 Ga-DOTATATE or 68 Ga-PSMA-11 PET-CT. Within this subgroup, seven out of 74 patients (9.45%) were eligible for 177 Lu-DOTATATE therapy, and nine out of 74 patients (12.16%) were eligible for 177 Lu-PSMA-targeted therapy. Four patients were eligible for both therapies. Among thyroglobulin elevation and negative iodine scintigraphy patient's subgroup, 9.45% could qualify for 177 Lu-DOTATATE and 12.16% for 177 Lu-PSMA-617. Four were eligible for both therapies. Given the lack of effective therapies, this subset of patients warrants consideration for radionuclide therapy exploration.

Stereotactic DOTATATE Positron Emission Tomography/Computed Tomography–Guided Resection of a Multiply Recurrent World Health Organization Grade 2 Parasagittal Meningioma: A Technical Case Report

BACKGROUND AND IMPORTANCE: Resection of parasagittal meningiomas is challenging due to venous and superior sagittal sinus involvement. Recurrent tumors can be particularly challenging given scar tissue from prior surgery and radiation, which can be difficult to differentiate from active tumor on preoperative MRI. Cu-64-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE) is a somatostatin receptor (SSTR) ligand detectable on positron emission tomography (PET) imaging. SSTR is expressed by most meningiomas. While DOTATATE-PET has been investigated for radiotherapy planning, its use in guiding oncological meningioma resection is understudied. Here, we present a case example demonstrating its use in guiding surgical planning and maximizing the extent of resection. CLINICAL PRESENTATION: A 45-year-old man with a World Health Organization grade 2 bilateral parasagittal meningioma presented with recurrence after 2 prior resections, wound infection and washout, and fractionated radiotherapy with boost to residual disease. Preoperative angiography demonstrated an occluded sagittal sinus beyond the extent of the residual tumor. Stereotactic DOTATATE PET-computed tomography (CT) imaging was integrated with the neuro-navigation and used intraoperatively to identify extent of active tumor, differentiating it from scar tissue and gliosis. This was used to facilitate oncological tumor resection with negative pathological margins that correlated with the absence of DOTATATE signal. CONCLUSION: Stereotactic DOTATATE PET-CT is a valuable addition to the neurosurgeon's toolkit, particularly when integrated into the neuro-navigation, for achieving complete resections of recurrent meningiomas, or meningiomas where the extent of tumor invasion can be challenging to define on preoperative MRI.

Comparison of Whole-Body Ga-68 DOTA TATE Positron Emission Tomography and Magnetic Resonance Imaging in the Detection of Bone Metastasis of Neuroendocrine Tumor in Simultaneous 3T Positron Emission Tomography/Computed Tomography

Comparison of Whole-Body Ga-68 DOTA TATE Positron Emission Tomography and Magnetic Resonance Imaging in the Detection of Bone Metastasis of Neuroendocrine Tumor in Simultaneous 3T Positron Emission Tomography/Computed Tomography

Advanced imaging and theranostics in thyroid cancer.

Thyroid cancers are endocrine neoplasms with diverse gene expression and behavior, for which constantly evolving anatomic and functional imaging/theranostic agents have an essential role for diagnosis, staging, and treatment. To achieve definitive diagnosis, neck ultrasound and associated risk stratification systems, notably Thyroid Imaging Reporting and Data System (TI-RADS), allow improved thyroid nodule characterization and management guidance. Radioactive iodine-131 (RAI) has long played a role in management of differentiated thyroid cancer (DTC), with recent literature emphasizing its effectiveness for intermediate-high risk cancers, exploring use of dosimetry for personalized medicine, and potential for retreatment with RAI following tumor redifferentiation. Iodine-124 positron emission tomography/computed tomography (PET/CT) has promising application for DTC staging and dosimetry. F18-fluorodeoxyglucose (FDG) PET/CT is used for staging of high risk DTC and identification of noniodine-avid disease recurrences, with metabolic uptake consistently portending poor prognosis. Poorly differentiated and anaplastic thyroid cancers are best assessed with anatomic imaging and F18-FDG PET/ CT, though recent studies show a potential theranostic role for Ga68/Lu177-prostate-specific membrane antigen. Medullary thyroid cancers are evaluated with ultrasound, CT, magnetic resonance imaging, and various positron-emitting radiotracers for PET imaging (F18-DOPA, F18-FDG, and recently Ga68-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE)); the latter may enable treatment with Lu177-DOTATATE. Multidisciplinary collaboration is essential to streamline appropriate management, given the wide array of available imaging and new therapies for metabolic and genetically complex cancers.

Normal Variants, Pitfalls and Artifacts in Ga-68 DOTATATE PET/CT Imaging.

Indium 111 DTPA Octreotide (Octreoscan) has been the pillar of Somatostatin receptor (SSTRs) imaging in nuclear medicine for over three decades. The advent of PET/CT brought new analogs of somatostatin that have higher affinity and improved resolution due to their labeling to Gallium 68 for positron imaging. The most used analogs include DOTATATE, DOTATOC and DOTANOC. However, Gallium 68-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE) is probably the most common non-FDG (fluoro-2-deoxy glucose) PET tracer alongside PSMA (prostate specific membrane antigen). In contrast to F18-labeled FDG, it does not require proximity to a cyclotron due to the availability of the Ga68 generator. DOTATATE is a somatostatin analog which allows whole body imaging of somatostatin receptors on cell surfaces. 68Ga-DOTA compounds provide the imaging standard for well-differentiated (Grade 1 and low grade 2) neuro-endocrine tumors (NETs) and is utilized in the staging and characterization and restaging of patients with NETs. 68Ga DOTATATE has a complementary role with 18F-FDG where tumors may exhibit varying degrees of differentiation. It furthermore has application as a prelude to therapy in selecting patients for peptide receptor radionuclide therapy using a theranostic approach. A sound knowledge of the normal biodistribution of the radiotracer is imperative for optimal patient outcome and to avoid potential false positives such as inflammation, normal pancreatic uncinate process uptake and osteoblastic activity. In this review, we will describe the normal appearances of the 68Ga DOTATATE and the potential pitfalls with the support of images to aid in improving interpretation of this crucial innovative tool in the management of individuals with tumors expressing SSTRs.

Diverse Manifestation of Acromegaly With Suspicion of Ectopic GHRH Secretion. Report of Two Cases

Introduction: Acromegaly can rarely be caused by an ectopic production of GH or GHRH by various neoplasms, most commonly neuroendocrine tumors of pancreatic or pulmonary origin. Squamous cell carcinoma of the lung has not been associated with ectopic GHRH secretion yet. The authors present two cases of acromegaly with suspicion of GHRH ectopy. Presentation of the Cases: Case 1. A male born in 1945 presenting with typical morphologic features of acromegaly. Pituitary MRI revealed a cuneatic-shaped, hypointense focal lesion (8x7x6 mm) in the right posterior part of the anterior pituitary lobe, radiologically interpreted as either hyperplasia of the intermediate lobe or atypical adenoma in a normal-sized pituitary. IGF-1 and no suppression of GH secretion after oral glucose load were observed. Furthermore, a polycyclic tumor in the 2nd segment of the right lung with pathological metabolic activity in 18FDG- PET/CT was discovered. Ga68- DOTA TATE PET/CT revealed no pathological accumulation of the tracer. After upper right lobectomy, squamous cell carcinoma, non-keratinizing, G3, with a negative immunohistochemical reaction for GH was confirmed. IHC for GHRH and serum GHRH have been scheduled. After surgery and chemotherapy, no biochemical remission of acromegaly was observed and the pituitary MRI showed stable radiological image of the pituitary tumor, suggesting rather a possible metastasis to the pituitary. Due to unfavorable prognosis, the patient was disqualified from neurosurgical resection of the pituitary tumor. Case 2. a male born in 1948 with typical symptoms of acromegaly, elevation of IGF-1 and no suppression of GH in OGTT. Due to MRI contraindications, only CT of the head was performed- it revealed partially empty sella, compressed pituitary with maximal diameter 3 mm and no focal lesions. Treatment with somatostatin analogue was introduced, however, only partial biochemical control was achieved. Ga68- DOTA TATE PET/CT performed after 8 years showed pathological expression of somatostatin receptors in the pancreatic tail. Abdominal CT confirmed a focal lesion in this location, 14x9 mm, with a strong enhancement after contrast administration, suggesting a neuroendocrine tumor. The patient refused to undergo any invasive procedures and remains treated with SRL. Serum GHRH has been scheduled. Conclusion: The authors report two cases of ectopic acromegaly suspicion, with an ambiguous clinical and radiological presentation. In unclear cases of acromegaly, ectopic production of GHRH should be taken into consideration.

Tumor Induced Osteomalacia - Long Term Medical Treatment When Surgery Is Risky

Introduction: Tumor induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by bone pain, muscle weakness and fractures caused by production of a phosphaturic factor by rare mesenchymal bone or soft tissue tumors that causes isolated renal phosphate loss and osteomalacia. Low phosphate (iP), high bone alkaline phosphatase (BAP), and normal or low 125 dihydroxy D, are salient biochemical findings. Fibroblast derived growth factor (FGF 23) may be high or inappropriately normal. Gallium-68 Dotatate (DoT) imaging has become the imaging method of choice. Long term medical management may be required when removal of the tumor is risky or not feasable. Case Report: 65 yr old woman with carcinoid tumor of the right lung and a bony lesion in the T3 vertebral body diagnosed with TIO. She was initially screened for osteoporosis after traumatic rib fractures. Bone scan and SPECT-CT revealed numerous foci of increased uptake. She had elevated alkaline phosphatase 186 IU/L (0–140) and PTH 83 pg/ml (15–65) with a low phosphate 1.5 mg/dl (2.5–4.5), along with normal FGF23 level 102 RU/ml Ref Range < + 180 RU/ml. DoT and PET CT imaging for TIO evaluation showed a foci of increased uptake right lower lobe of her lung, and “osseous metastatic disease” in the right scapula, vertebral body, iliac, and pubic ramus. Sclerosis of T3 vertebral body was noted in the area of intense Gallium Dotatate uptake. Transbronchial excision of the lesion showed a well differentiated neuroendocrine carcinoma. Chromogranin A and 24 hour urine for 5HIAA were normal. She responded well to medical therapy with oral phosphate, calcium and calcitriol. Follow up, DoT and FDG PET showed persistent intense uptake in the sclerotic lesion on T3 vertebral body, while the rest of the hot spots resolved. Sclerotic T3 lesion is likely the primary lesion that is responsible for the TIO. Neuroendocrine tumor of the lung may be a mere association. Biopsy of the T3 lesion was not feasible and excision was considered risky to the patient. Discussion: Our case illustrates that awareness is the key to early diagnosis of TIO. FGF 23 in some TIO cases may be inappropriately normal in commercial assays and even in research labs. Measurement of fibronectin 1 (FN1) and FGF receptor 1 fusion gene which is noted in up to 60% of tumors are not commercially available. While DoT and PET CT are imaging modality of choice, CT and MRI may be useful to define the anatomy of the lesion. Long term medical management may be necessary when removal of primary lesion is not possible or risky. Most tumors are benign while some may prove to be malignant.

Chilean experience using “Theranostics” for treating metastatic neuroendocrine tumors with [177Lu]Lu DOTA-TATE

Introduction: Well-differentiated, Neuroendocrine Tumors (NET) are highly heterogenic and slow-growing pathologies, characterized by unspecific symptomatology and elevated expression of somatostatin receptors (SSTR). Despite the high incidence of NETs, several patients are diagnosed in advance stages of the disease when surgery is insufficient to treat the pathology. Peptide receptor radionuclide therapy (PRRT) has emerged as a new state-of-the-art treatment for NET-patients in advanced stages. Results: In this retrospective study, between 2004 and 2018 a total of 66 patients with advanced-stage-NETs, refractory to other therapies, were treated with [177Lu]Lu DOTA TATE. At the end of the study, 56.1% of the patients were alive and the median overall survival for all patients in the study was 86.3 months. Patients that received doses ≥ 22.2 GBq showed increased overall survival (OS) in comparison with patients that received doses &lt; 22.2 GBq (HR, 0.168; 95%CI 0.12- 0.99; p&lt;0.001), adjusted by gender. Likewise, patients that received doses ≥29.6 GBq had an increased OS (HR, 0.42; 95%CI 0.19-0.94, p&lt;0.05). Conclusion: Although several studies have shown that PRRT is an effective alternative for advanced NET, patients in South America have no regular access to PRRT. Our study proves that [177Lu]Lu-DOTA-TATE effectively increases the survival of patients with metastatic NET and provides an excellent alternative in terms of cost-efficiency for South American countries.

Sheffield experience of administering Lutathera as a day case treatment

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Application progress of radionuclide imaging and therapy in neuroendocrine tumors

Some subtypes of somatostatin receptors (SSTRs) are overexpressed in neuroendocrine tumors (NETs). 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-D-Phel-Tyr3-Thr8-octreotide (DOTATATE) is a somatostatin analogue that can be combined with somatostatin receptor specifically, which plays an important role not only in early diagnosis, clinical staging, treatment guiding, recurrence detection and metastasis of NETs, but also in the targeted radionuclide therapy of tumors. The side effect of peptide receptor radionuclide therapy is relatively mild, which is of great clinical significance for prolonging patients′ survival, improving symptoms and the quality of life. Key words: Neuroendocrine tumors; DOTATATE; Lutetium; Trends

Comparison of DOTA and NODAGA as chelates for 68Ga-labelled CDP1 as novel infection PET imaging agents

The cathelicidin-derived peptide (CDP1) is a human antimicrobial peptide that preferentially targets bacterial membranes in response to infection. CDP1 was functionalised with NODAGA and DOTA for complexation with gallium-68 to evaluate its potential as an infection imaging tracer. The synthesis of [68Ga]Ga–NODAGA–CDP1 and [68Ga]Ga–DOTA–CDP1 were optimised for pH, molarity, incubation time and temperature, and product purification. The integrity and protein binding were investigated employing [68Ga]GaCl3 and [68Ga]Ga–DOTA–TATE as internal references. [68Ga]Ga–NODAGA–CDP1 displayed good labelling properties with higher product yield compared to [68Ga]Ga–DOTA–CDP1. In contrast, [68Ga]Ga–DOTA–CDP1 showed better stability and is the preferred candidate for an in vivo investigation.

Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET

Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET

Impact of Ga-68 DOTATATE scan on clinical management of neuroendocrine tumor patients (NET): A single center review of 200 Scans.

e16187Background: Gallium 68 dotatate (DOTA) scanning provides physiologic imaging and assists in the localization of disease in somatostatin receptor positive NET patients (pts). Questions regardi...

Lu177-DOTA-octreotate therapy on neuroendocrine tumour management: A case report and literature review

Favourable outcomes of peptide receptor radiotherapy of neuroendocrine tumors have been reported during the last years. This case report refers to a patient with a non-functional neuroendocrine carcinoma of pancreas with liver metastases and abdominal lymph nodes involvement. He underwent fractionated treatment with 4 cycles of Lu 177 -DOTA-octreoate (7.400MBq) after the failure of treatment with chemotherapy regiments. We conclude that fractionated therapy with Lu 177 -DOTA-octreotate should be considered a treatment option in the management of patients for symptomatic improvement in inoperable or metastasized neuroendocrine tumors, and for patients with large tumors and high somatostatin receptor expression.

Erdheim Chester Hastalığı Olan Dört Olgunun Nükleer Tıp Görüntüleme Yöntemlerindeki Heterojen Bulguları

Erdheim-Chester disease (ECD) is an uncommon, sporadic, non-Langerhans cell histiocytosis characterized by xanthomatous or xanthogranulomatous histiocyte infiltration of affecting both bone and soft tissue systems. Herein we report the imaging features of four cases of ECD who had different multiorgan manifestations. The nuclear medicine imaging modalities consisting of technetium-99m methylene-diphosphonate (Tc-99m MDP) scintigraphy, Fluorine-18 2-deoxy-2-fluoro-D-glucose positron emission tomography/computed tomography (F-18 FDG PET/CT) and Ga-68 DOTA-octreotate (DOTA-TATE) PET/CT are useful methods to determine the ordinarily and extraordinarily heterogeneous clinical manifestations of ECD.

Metastatic Neuroendocrine Tumor with Extensive Bone Marrow Involvement at Diagnosis: Evaluation of Response and Hematological Toxicity Profile of PRRT with (177)Lu-DOTATATE.

The aim of this study was to evaluate the response and hematological toxicity in peptide receptor radionuclide therapy (PRRT) with lutetium (177Lu)-DOTA-octreotate (DOTATATE) in metastatic neuroendocrine tumor (NET) with extensive bone marrow metastasis at the initial diagnosis. A retrospective evaluation was undertaken for this purpose: Patients with NET with extensive diffuse bone marrow involvement at diagnosis who had received at least three cycles of PRRT with 177Lu-DOTATATE were considered for the analysis. The selected patients were analyzed for the following: (i) Patient and lesional characteristics, (ii) associated metastatic burden, (iii) hematological parameters at diagnosis and during the course of therapy, (iv) response to PRRT (using a 3-parameter assessment: Symptomatic including Karnofsky/Lansky performance score, biochemical finding, and scan finding), (v) dual tracer imaging features [with somatostatin receptor imaging (SRI) and fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)]. Based on the visual grading, tracer uptake in somatostatin receptor (SSTR)-positive bone marrow lesions were graded by a 4-point scale into four categories (0-III) in comparison with the hepatic uptake on the scan: 0 - no uptake; I - clear focus but less than liver uptake; II - equal to liver uptake; and III - higher than liver uptake]. Hematological toxicity was evaluated using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 score. A total of five patients (age range: 26-62 years; three males and two females) with diffuse bone marrow involvement at the diagnosis was encountered following analysis of the entire patient population of 250 patients. Based on the site of the primary, three had thoracic NET (two patients bronchial carcinoid and one pulmonary NET) and two gastroenteropancreatic NET (one in the duodenum and one patient of unknown primary with liver metastasis). Associated sites of metastases included the liver (n = 5), breast (n = 1), and aortocaval nodes (n = 1). On baseline diagnostic study [68 Ga-DOTANOC/TATE or the technetium (99mTc)-hydrazinonicotinamide (HYNIC)-tektrotyd (TOC)], tracer uptake in the bone marrow in all patients was Grade III. At the time of analysis, the patients received three to four cycles of PRRT and a cumulative dose of 16.1-25.6 GBq with a follow-up duration ranging 10-27 months. The response as assessed by three parameters: (i) Symptomatic: All patients (except for one) reported excellent symptomatic palliation and better quality of life with improvement of Karnofsky/Lansky scores; the single case with nonresponse had shown symptomatic response in the initial 6 months following which he had a progressive disease and death at 18 months (ii) biochemical: Three patients had shown more than 50% reduction in the serum chromogranin level, one had shown increase but had demonstrated clinical evidence of response with radiologically stable disease while the other who had shown slight increase of chromogranin A (CgA) level had shown progressive disease thereafter (iii) radiological: Three patients demonstrated partial response (on FDG-PET/CT), one patient had stable disease and one patient had progressive disease following initial clinical response. As per the NCI-CTCAE score, only one patient had persistent Grade I anemia without any deterioration with the administered dose at the time of analysis. FDG uptake in the bone marrow metastatic lesions showed no obvious FDG avidity on visual assessment except for two patients (low-grade FDG uptake). Interestingly, the associated metastatic lesions [except for patient I with Mib1 labeling index (LI): 1-2%], demonstrated high FDG avidity. Thus, we observed that the majority (in our series four out of five patients, i.e. 80%) of the patients had excellent symptomatic response with at least stabilization of the disease at a follow-up period of 10-27 months. The single patient who had a progressive disease also had a good symptomatic response in the initial 6 months from the first dose of PRRT. Despite the extensive bone marrow involvement, no hematological toxicity was observed (only one patient showed Grade I anemia), suggesting that PRRT is well-tolerated by this particular subgroup.

An intrapatient comparison of 99Tcm-HYNIC-TOC imaging and 68Ga-DOTA-TATE imaging on patients with gastroenteropancreatic neuroendocrine neoplasms

Objective To compare the diagnostic performances of 99Tcm-HYNIC-TOC SPECT and 68Ga-DOTA-TATE PET/CT on patients with gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). Methods From May 2013 to February 2014, 34 patients (17 males, 17 females; age: 23-75 years) with histologically proven GEP-NEN were enrolled in the study. All patients underwent 99Tcm-HYNIC-TOC SPECT imaging and 68Ga-DOTA-TATE PET/CT imaging. χ2 test and two-sample t test were used to analyze the data. Results The positive rate of 99Tcm-HYNIC-TOC imaging was 58.8%(20/34), which had no statistical difference with that of 68Ga-DOTA-TATE imaging (70.6%, 24/34; χ2=2.25, P>0.05). However, taking lesions as the target, the detection positive rate of 68Ga-DOTA-TATE imaging (15.7%, 48/306) was statistically higher than that of 99Tcm-HYNIC-TOC imaging (9.5%, 29/306; χ2=17.50, P<0.05), especially for the lymph nodes, liver and skeleton lesions. For the liver lesions, the short diameter and SUVmax of 99Tcm-HYNIC-TOC positive lesions in the liver were statistically higher than those of negative lesions (t=4.4 and 3.2, both P<0.05). Conclusion Compared with 99Tcm-HYNIC-TOC scintigraphy, 68Ga-DOTA-TATE PET/CT imaging shows a significantly higher detection rate on small or structure-complex lesions on GEP-NEN patients. Key words: Neuroendocrine tumors; Tomography, emission-computed, single-photon; Tomography, emission-computed; Tomography, X-ray computed; Technetium; Gallium radioisotopes; HYNIC-TOC; DOTA-TATE

Clinical value of 68Ga-DOTATATE PET/CT in pituitary adenoma: a pilot study

Objective To investigate the correlation between the uptake of 68Ga-DOTATATE in pituitary adenoma and clinical parameters such as hormonal hypersecretion, and to evaluate the curative effect with 68Ga-DOTATATE imaging after octreotide therapy in patients with growth hormone-secreting adenoma (GH adenoma). Methods A total of 34 patients (15 males, 19 females) with pituitary adenoma were recruited, including 5 adrenocorticotropic hormone-secreting adenoma (ACTH adenoma), 17 GH adenoma, and 12 non-functioning adenoma (NF adenoma). In the 17 patients with GH adenoma, there were 13 patients treated by octreotide intramuscular injection 3 times with a total dose of 60 mg for 3 months. The finial diagnosis was based on histology. 68Ga-DOTATATE imaging was performed, and SUVmean, tumor volume and density index (DI) were recorded in all patients. The DI was the ratio of tumor SUVmean to tumor volume. The effective therapy was defined as more than 50% of hormonal suppression or more than 20% of tumor shrinkage. Non-parametric Mann-Whitney u test was used. Results NF adenoma showed greater tumor volume than secretory adenoma, ((9.10±7.00) cm3vs (2.92±1.60) cm3,u=43.0, P<0.05), whereas DI of secretory adenoma was higher than that of NF adenoma (7.16±4.52 vs 1.08±1.40, u=48.5, P<0.05). Additionally, DI was significantly higher(3.55±0.91 vs 1.38±0.69, u=2.0, P<0.05) in patients (n=8) with effective treatment than that in patients without effective treatment (n=5). Conclusion 68Ga-DOTATATE may be a useful probe for PET imaging in patients with pituitary adenoma, and may be valuable for predicting the therapeutic effect of somatostatin analog treatment. Key words: Pituitary neoplasms; Gallium radioisotopes; Tomography, emission-computed; Tomography, X-ray computed; DOTATATE

Synthesis and in vivo evaluation of 68Ga-DOTATATE in mice

Objective To synthesize 68Ga-1, 4, 7, 10-tetraazacyclododecane-N, N', N″, N-tetraacetic acid-D-Phe1-Tyr3-Thr8-octreotide (68Ga-DOTATATE) manually and automatically, validate its qualities in vitro, and evaluate its biodistribution in ICR mice and the microPET imaging in nude mice bearing pancreatic AR42J tumor. Methods 68Ga-DOTATATE was synthesized by automatic method using commercial metal isotope multifunctional module with strong cation exchange(SCX) column and by manual method. Both the products were measured for quality control. For the biodistribution study 5 groups of ICR mice were injected with 68Ga-DOTATATE(1.11 MBq) and executed at 10, 30, 60, 120 and 240 min postinjection, respectively. The organs were weighted, and %ID/g was calculated. Nude mice bearing pancreatic AR42J tumor were intravenously injected with 3.7 MBq 68Ga-DOTATATE, and then microPET imaging was acquired at 10, 30, 60, 120, 18 and 240 min. Results 68Ga-DOTATATE could be successfully synthesized by the automatic and manual methods. Both the product injections were colorless and clear. The pH value was 6.5±0.1. For the products obtained from the two methods, the radiochemical purities were over 99%, and the products were stable for 4 h at room temperature. For the automatic method, 68Ga-DOTATATE was synthesized within 30 min and with the radiochemical yield of (51.8±3.2)% (time decay corrected) . For the manual method, the time used for the synthesis was 20 min, and the labeling yield was over 99%. Three batches of the products were aseptic and pyrogen-free. In ICR mice, 68Ga-DOTATATE was excreted by the kidney, and showed relatively high accumulation in the liver, spleen, pancreas and adrenal glands, while lower in the bone and soft tissue. The clearance from blood was fast with (4.41±0.81) %ID/g at 10 min postinjection and (0.78±0.32) %ID/g at 1 h. MicroPET imaging showed increased uptake of 68Ga-DOTATATE in the tumor tissues, and T/NT were 2.01±0.29(10 min), 6.74±2.90(30 min) and 4.46±2.05(60 min), respectively. Conclusions 68Ga-DOTATATE could be successfully synthesized manually and automatically. The products reach to the specification of radioactive drugs and could be used as an attractive positron emitting radiotracer for detection of the somatostatin receptor-positive tumors. Key words: DOTATATE; Isotope labeling; Gallium radioisotopes; Chemical synthesis; Tomography, emission-computed; Mice, nude

Erratum to: Twins in spirit: DOTATATE and high-affinity DOTATATE

Erratum to: Twins in spirit: DOTATATE and high-affinity DOTATATE