Imaging Characteristics of 68Ga-DOTATATE PET/CT in Tumor-Induced Osteomalacia / 罕见病研究

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumors secreting fibroblast growth factor 23 (FGF23) that promotes urinary phosphorus excretion. Thus, TIO is typically characterized by phosphoruria, hypophosphatemia, and osteomalacia. Diagnosis and localization of the tumor is often difficult due to its small size, slow growth and concealed location. Due to the high expression of somatostatin receptors in pathogenic tumors, nuclear medicine functional imaging, particularly somatostatin receptor imaging, is used for diagnosis and localization of culprit tumors with high sensitivity and specificity. Here we retrospectively analyze 25 cases in which 68Ga-DOTATATE PET/CT successfully localized and diagnosed TIO culprit tumors. The clinical features, pathological results and image characteristics of 68Ga-DOTATATE PET/CT imaging were analyzed and compared with other imaging diagnostic techniques. It was confirmed that 68Ga-DOTATATE PET/CT imaging was the preferred imaging technique for successful diagnosis and localization of TIO pathogenic tumors.

Detection of Neuroendocrine Tumour of Sphenoid Sinus on the Gallium-68 DOTATATE PET/CT: A Rare Entity

@#Neuroendocrine tumours (NETs) are a category of neoplasm that is characterised by its phenotypic and heterogeneity. The occurrence of this type of neoplasm in the nasal cavity and paranasal sinuses is extremely rare accounting for only 0.2-0.8% of all cancers. NET tends to expresses somatostatin receptors (SSTR) and owning to this unique characteristic, molecular imaging has been able to detect these tumours using radiolabelled somatostatin analogue agent. Gallium-68 (Ga-68) DOTATATE PET/CT is an example of SSTR imaging and has been shown to be of importance in the assessment and staging of NET. We present a case of a rare sphenoid sinus NET in a 45-year-old gentleman whom initially presented with persistent left eye pain which led to visual loss. We described the utilization of Ga-68 DOTATATE PET/CT in the diagnosis and staging of this patient which in turn dictated treatment approach.

Estimation of renal absorbed doses in the treatment of neuroendocrine tumors using 177Lu-DOTA-TATE / 中华放射医学与防护杂志

Objective:To estimate the renal absorbed dose in the treatment of neuroendocrine tumors using 177Lu-DOTA-TATE and to assess the radiation safety and guide the treatment. Methods:The dosimetric calculations of patients treated with 177Lu-DOTA-TATE were carried out based on planar images of single photon emission computed tomography (SPECT). The regions of interest (ROIs) of the whole body and kidneys were delineated and converted into activity. Accordingly, the time-activity curves of the ROIs were obtained. The effective half-lives and cumulative activity of ROIs were calculated through the fitting of a single exponential equation of the ROIs. Then the absorbed doses were calculated based on the medical internal radiation dosimetry (MIRD) formalism. Results:A total of 11 patients with neuroendocrine tumors received 18 cycles of treatments with 177Lu-DOTA-TATE. The effective half-lives of 177Lu-DOTA-TATE in the whole body and kidneys were 20.0-99.8 h and 38.2-75.2 h, respectively, with an average of (57.3 ± 21.4) h and (53.1 ± 12.5) h, respectively. The renal absorbed doses of 177Lu-DTA-TATE were 0.25-1.48 mGy/MBq, with an average of (0.90 ± 0.31) mGy/MBq. The minimum and maximum renal absorbed doses in a single treatment cycle were 1.8 Gy and 9.6 Gy, respectively, while the maximum renal absorbed dose in multiple treatment cycles was 21.7 Gy. Conclusions:The renal absorbed doses in the treatment of neuroendocrine tumors using 177Lu-DOTA-TATE were estimated. The result indicate that the renal absorbed doses were lower than the tolerable dose limits. This study is expected to guide the precise treatment of neuroendocrine tumors.

Application progress of radionuclide imaging and therapy in neuroendocrine tumors / 中华核医学与分子影像杂志

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.

The first application of Ga-68 and Lu-177 theranostics in the Philippines: A rare case of mediastinal small cell neuroendocrine carcinoma

@#A 43-year-old female with a surgically unresectable and non-secretory mediastinal small cell neuroendocrine carcinoma waws previously given the protein kinase inhibitor Everolimus with intolerable nausea and fatigue. High somatostatin receptor expression of the known tumor was seen on 68Ga-DOTATATE PET/CT scan. She was then given 6.4 GBq of 177 Lu-DOTATATE with no adverse events. A follow-up 68Ga-DOTATATE PET/CT scan three months post-treatment showerd stable DOTATATE affinity with no evidence of metastasis. this case presents an overview of peptide receptor radionuclide therapy (PRRT), especially for multidisciplinary teams in the Philippines, as 68Ga and 177 Lu theranostics is introduced in the country.

Eruption of Metastatic Paraganglioma After Successful Therapy with ¹⁷⁷Lu/⁹⁰Y-DOTATOC and ¹⁷⁷Lu-DOTATATE / 대한핵의학회잡지

Metastatic paraganglioma treatment options are limited. Peptide receptor radionuclide therapy (PRRT) has been introduced as a novel management option for metastatic neuroendocrine tumors demonstrating safety, efficacy, and increased quality of life.We present two cases of marked progression of metastatic paraganglioma following initial partial response to PRRT. Given their positivity on ⁶⁸Ga-DOTATATE PET/CT and ¹¹¹In-octreotide SPECT, they underwent PRRT. Imaging following treatment revealed significant improvement in size and intensity, with some foci nearly completely resolved in one patient, and disease regression with a decrease in the number and size of bone and liver lesions in the second patient.Within months, repeat imaging in both patients revealed extensive metastatic disease with new lesions, which eventually lead to their deaths. The mechanism for rapid disease progression after partial response is not well understood, although it could be related to initially high Ki-67 levels or ¹⁸F-FDG PET/CT SUV(max) values. However, naturally rapid disease progression despite PRRT response cannot be excluded. This finding warrants the importance of proper patient counseling along with early and accurate pre-PRRT assessment, taking into consideration the above potential risk factors for therapy response in order to personalize treatment regimens and achieve maximum patient benefit.

Gallbladder Paraganglioma Associated with SDHD Mutation: a Potential Pitfall on ¹⁸F-FDOPA PET Imaging / 대한핵의학회잡지

A 36-year-old male patient initially presented with hypertension, tinnitus, bilateral carotid masses, a right jugular foramen, and a periaortic arch mass with an elevated plasma dopamine level but an otherwise normal biochemical profile. On surveillance MRI 4 years after initial presentation, he was found to have a 2.2-cm T2 hyperintense lesion with arterial enhancement adjacent to the gallbladder, which demonstrated avidity on ⁶⁸Ga-DOTATATE PET/CTand retrospectively on ¹⁸F-FDOPA PET/CT but was nonavid on ¹⁸F-FDG PET/CT. Biochemical work-up including plasma catecholamines, metanephrines, and chromogranin A levels were found to be within normal limits. This lesion was surgically resected and was confirmed to be a paraganglioma (PGL) originating from the gallbladder wall on histopathology. Pheochromocytoma (PHEO) and PGL are rare tumors of the autonomic nervous system. Succinate dehydrogenase subunit D (SDHD) pathogenic variants of the succinate dehydrogenase complex are usually involved in parasympathetic, extra-adrenal, multifocal head, and neck PGLs. We report an unusual location of PGL in the gallbladder associated with SDHD mutation which could present as a potential pitfall on ¹⁸F-FDOPA PET/CT as its normal excretion occurs through biliary system and gallbladder. This case highlights the superiority of ⁶⁸Ga-DOTATATE in comparison to ¹⁸F-FDOPA and ¹⁸F-FDG in the detection of SDHD-related parasympathetic PGL.ClinicalTrials.gov Identifier: NCT00004847.

The Emergence of Theranostics in the Philippines: Overcoming Challenges and Bringing Hope / 대한핵의학회잡지

Medical managements are becoming personalized while diseases are being understood at the molecular level. Nuclear medicine is one of the fields actively contributing to this development. In particular, theranostics, a combinatorial term for therapy and diagnostics, enables accurate imaging and subsequent targeted radionuclide treatment. Due to its high impact in healthcare, many countries have begun to offer Ga-68 PET/CTscans and Lu-177 therapies. The Philippines has followed suit through the initiative of this author and able support of the administration and staff of St. Luke's Medical Center. The Ga-68 DOTATATE and PSMA PET/CT scans became officially available in January 2018 while the first peptide receptor radionuclide therapy for neuroendocrine tumor and first PSMA radioligand therapy for prostate cancer occurred in May and June 2018, respectively. Amidst past, present, and future challenges, theranostics has emerged in the Philippines, offering hope to cancer patients in the country.

Nuclear Medicine Theranostics: Perspective from Pakistan / 대한핵의학회잡지

Nuclear medicine has been offering diagnostic and therapeutic solution since the introduction of radioactive iodine for thyroid diseases since decades. However, the concept of theranostics has given a new found impetus to the use of pairs of radiopharmaceuticals for diagnosis and treatment. Presented here is a perspective on theranostics from Pakistan.

Application progress of radionuclide imaging and therapy in neuroendocrine tumors / 中华核医学与分子影像杂志

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-octreoti-de ( 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 de-tection 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.

Incidental Detection of Parathyroid Adenoma on Somatostatin Receptor PET/CT and Incremental Role of ¹⁸F-Fluorocholine PET/CT in MEN1 Syndrome / 대한핵의학회잡지

Multiple endocrine neoplasia type 1 (MEN1) syndrome is characterized by combined occurrence of tumors of endocrine glands including the parathyroid, the pancreatic islet cells, and the anterior pituitary gland. Parathyroid involvement is the most common manifestation and usually the first clinical involvement inMEN1 syndrome, followed by gastroentero-pancreatic neuroendocrine tumors (NETs). Here we present a case where the patient initially presented with metastatic gastric NET and a single parathyroid adenoma was detected incidentally on ⁶⁸Ga-DOTANOC PET/CT done as part of post ¹⁷⁷Lu-DOTATATE therapy (PRRT) follow-up. Further ¹⁸F-fluorocholine PET/CT showed four adenomas for which the patient subsequently underwent subtotal parathyroidectomy.

Patologías benignas y variantes que captan 68Ga-DOTATATE en PET/TC / Benign Pathology And Variants With Uptake In 68ga-Dotatate Pet/Ct Studies

Objetivos: Valorar las variantes fisiológicas, anatómicas y lesiones benignas en estudios por tomografía computada por emisión de positrones (PET/TC) con Galio 68 (68Ga)-DOTATATE. Materiales y métodos: Se revisaron en forma retrospectiva los informes de PET/TC con 68Ga-DOTATATE y se seleccionaron aquellos en los cuales se mencionaran palabras en el reporte relacionadas a variantes anatómicas, fisiológicas y tumores benignos. El grado de captación del 68Ga-DOTATATE fue evaluado de forma cualitativa y cuantitativa mediante la medición del valor estandarizado de captación máximo (SUVmax). Se consignó la localización del hallazgo, el valor de SUVmax y la imagen morfológica por tomografía computada (TC). Todos los casos fueron controlados mediante evolución clínica y hallazgos imagenológicos. Resultados: De un total de 772 informes de PET/TC se obtuvo un total de 28 pacientes con 33 variantes o tumores benignos, 14 mujeres y 14 hombres con edad promedio de 63 años. Las captaciones se clasificaron en cuatro grupos: variantes anatómicas y/o fisiológicas (n = 15), dependientes de la actividad osteoblástica (n=4), dependientes de actividad inflamatoria (n = 10) y tumores benignos no neuro-endócrinos (n = 4). Discusión: Los receptores de somatostatina se localizan no sólo en el sistema neuroendócrino sino también en otros tejidos. Las variantes fisiológicas, anatómicas y tumores benignos que expresan estos receptores pueden inducir a un error diagnóstico. Conclusión: Las variantes fisiológicas y lesiones benignas (tumorales e inflamatorias) pueden captar 68Ga-DOTATATE ya que sus tejidos pueden expresar receptores de somatostatina. El análisis semiológico del componente tomográfico de este método de imágenes híbrido, permite la orientación diagnóstica, optimizando el rendimiento del estudio PET/TC.

Purpose: To evaluate the physiological, anatomical variants and benign lesions in positrón emission computed tomography (PET/CT) studies with 68Ga-DOTATATE. Materials and methods: We retrospectively reviewed PET/CT reports scanned with 68Ga-DOTATATE and selected those that contained words in the report related to anatomical, physiological variants and benign tumors. The degree of 68Ga-DOTATATE uptake was evaluated qualitatively and quantitatively by measuring the standarized uptake max value (SUVmax value). The anatomical location, SUVmax value and morphological CT image findings were recorded. All cases had clinical and imaging follow-up. Results: From a total of 772 PET/CT reports, 28 patients were obtained with 33 benign variants or tumors, 14 females and 14 males with a median age of 63 years. Uptake patterns were classified into four groups: anatomic and physiological variants (15), dependent on osteoblastic activity (4), dependent on inflammatory activity (10) and non-neuro-endocrine benign tumors (4). Discussion: Somatostatin receptors are overexpressed not only in the neuroendocrine system but also in other tissues. Physiological, anatomical variants and benign tumors expressing these receptors may be misleading. In the present work the frequency of this finding is 5.1%. Conclusion: Physiological variants and benign lesions (tumor and inflammatory) can accumulate 68Ga-DOTATATE since their tissues can express somatostatin receptors. The semiologic analysis of the tomographic component of this hybrid method enhances the diagnostic efficacy, optimizing PET/CT study performance.

Terapia con [ 177 Lu - Dota0 - Tyr 3 ]-Octreotate ( 177 Lu-Dotatate) en pacientes con tumores avanzados de origen neuroendocrino: experiencia inicial y resultados preliminares / Therapy with [ 177 Lu - Dota0 - Tyr 3 ]-Octreotate ( 177 Lu-Dotatate) in Patients with Advanced Neuroendocrine Tumors: Initial Experience and Preliminary Results / Terapia com [ 177 Lu - Dota0 - Tyr 3 ]-Octreotate ( 177 Lu-Dotatate) em Pacientes com Tumores Avançados de Origem Neuroendócrino: Experiência Inicial e Resultados Preliminares

Resumen Objetivo: Mostrar la experiencia inicial y los resultados preliminares de la terapia con [177Lu -Dota0 - Tyr3] - Octreotate (177Lu-Dotatate) en pacientes tratados en la Fundación Cardioinfantil - Instituto de Cardiología (FCI-IC) debido a que la experiencia derivada de esta práctica en países latinoamericanos es poco conocida. Materiales y métodos: Se realizó un análisis descriptivo y retrospectivo en pacientes a los que se les realizó terapia con 177Lu-Dotatate con al menos una dosis y un año de seguimiento. Se incluyeron 8 pacientes (4 mujeres y 4 hombres) de edad media: 57 años (50-63). Se administraron 24 dosis en total, 3 dosis en promedio por paciente, 187 GBq totales y 23,5 GBq dosis/paciente. Se valoró la respuesta al tratamiento y la presencia de efectos adversos. Resultados: El tiempo medio de seguimiento fue de 46 meses (26-72 meses). 5/8 pacientes tenían diagnóstico de tumores neuroendocrinos (TNE) de origen pancreático, 2/8 de origen gástrico y 1/8 de yeyuno. 7/8 pacientes tenían compromiso metastásico; 1/8, a pesar de no tener afectación metastásica, fue considerado irresecable. 7/8 pacientes presentaron síntomas posterapia leves y 1/8 eventos adversos serios. 2/8 pacientes tuvieron respuesta parcial, 4/8 enfermedad estable y 2/8 respuesta completa. Sin embargo, al final del seguimiento un paciente que tuvo respuesta completa presentó recaída y otro, respuesta parcial con posterior progresión y muerte. Conclusiones: En la institución, la terapia con 177Lu-Dotatate ha sido segura y eficaz en pacientes con TNE como alternativa terapéutica con adecuados niveles de respuesta y control de la enfermedad con eventos adversos leves, esperables y eventos serios mínimos autolimitados.

Abstract Objective: To Show the initial experience and preliminary results of therapy with [177Lu -Dota0 - Tyr3] - Octreotate (177 Lu-Dotatate) in patients with neuroendocrine tumors (NET) treated in our institution, because the experience gained from this practice in Latin American countries is poorly known. Materials and methods: A descriptive and retrospective analysis in patients who have undergone therapy with 177 Lu-Dotatate with at least one dose and at least one year of follow-up was performed. 8 patients (4 women and 4 men) with a mean age of 57 years (50-63) were included. A total of 24 doses were given, an average of 3 doses per patient. A total of 187 GBq were administered, equivalent to 23.5 GBq / patient. Response to therapy and the presence of adverse short and long term effects were assessed. Results: The average follow-up time was 46 months (26-72 months). 5/8 patients were diagnosed with pancreatic net, 2/8 of gastric origin and 1/8 of small bowel origin. 7/8 patients had metastatic involvement and 1/8 patient despite not having metastasis was considered unresectable. 6/8 patients had mild post-therapy symptoms and 1/8 serious adverse events. 2/8 patients had partial response, 4/8 stable disease and 2/8 had a complete response. At the end of follow-up, however, one patient who had a complete response presented with recurrence and one with partial response showed progression and death. Conclusions: In our experience, therapy with 177 Lu-Dotatate was safe and effective in patients with net as an alternative therapy with appropriate levels of response and disease control and with mild expected adverse events and self-limiting minimum serious events.

Resumo Objetivo: Mostrar a experiência inicial e os resultados preliminares da terapia com [177Lu - Dota0 - Tyr3] -Octreotate (177Lu-Dotatate) em pacientes tratados na nossa instituição, devido a que a experiência derivada desta prática em países latino-americanos é pouco conhecida. Materiais e métodos: Se realizou uma análise descritiva e retrospectiva em pacientes aos que se lhes tem realizado terapia com 177Lu-Dotatate com ao menos uma dose e ao menos um ano de seguimento. Incluíram-se 8 pacientes, idade média de 57 anos (50-63). Administraram-se: 24 doses em total, 3 doses em média por paciente, 187 GBq totais administrados e 23.5 GBq doses/paciente. Valorou-se a resposta ao tratamento e a presença de efeitos adversos. Resultados: O tempo médio de seguimento foi de 45 meses (26-72 meses). 5/8 tinham diagnóstico de TNE de origem pancreática, 2/8 de origem gástrica e 1/8 de jejuno. 7/8 pacientes tinham compromisso metastático e 1/8 paciente apesar de não ter afetação metastática foi considerado irressecável. 6/8 pacientes apresentaram sintomas pós-terapia leves e 1/8 eventos adversos sérios. 2/8 pacientes tiveram resposta parcial, 4/4 doença estável e 2/8 resposta completa. No entanto, no final do seguimento um paciente que teve resposta completa apresentou recaída e outro resposta parcial com posterior progressão e morte. Conclusões: no nosso meio a terapia com 177Lu-Dotatate tem sido segura e eficaz em pacientes com TNE como alternativa terapêutica com adequados níveis de resposta e controle da doença com eventos adversos leves esperáveis e eventos sérios mínimos autolimitados.

Tratamento de tumores neuroendócrinos por medicina nuclear: revisão sistemática da eficácia e segurança do radiofármaco Dotatate-177Lu / Treatment of neuroendocrine tumors by nuclear medicine: a systematic review of efficacy and safety of the radiopharmaceutical 177Lu-Dotatate

O DOTATATE-177Lu é um análogo de somatostatina radiomarcado que guia a radioatividade para tumores neuroendócrinos (NETs) que superexpressam receptores de somatostatina (SSTRs), promovendo o seu tratamento por terapia radionuclídica receptor-específica (PRRT). O objetivo deste trabalho foi avaliar a eficácia e a segurança da PRRT dos NETs com o DOTATATE-177Lu, através de uma revisão sistemática da literatura. A PRRT com o DOTATATE-177Lu foi eficaz no tratamento de NETs metastáticos ou inoperáveis que expressam SSTR tipo 2. Observou-se estabilização ou até regressão da doença em 20 a 50 % dos casos. Já a prevalência de remissão total da doença, apesar de numericamente baixa, foi satisfatória, principalmente levando-se em conta o estágio avançado dos tumores. Os efeitos adversos mais comuns da PRRT foram toxicidade renal e hematológica. Apesar dos estudos evidenciarem a eficácia e a segurança da PRRT com o radiofármaco, essa terapia ainda é considerada em desenvolvimento.

The DOTATATE-177Lu is a radiolabeled somatostatin analogue that guides the radioactivity to neuroendocrine tumors (NETs) that overexpress somatostatin receptors (SSTRs), allowing their treatment by receptor- specific radionuclide therapy (PRRT). The aim of this study was to evaluate the efficacy and safety of PRRT of NETs with DOTATATE-177Lu through a systematic literature review. PRRT with 177Lu - DOTATATE was effective in the treatment of inoperable or metastatic NETs that express SSTR type 2. Stabilization or regression of the disease was observed in 20 to 50% of the cases . The prevalence of total remission, although numerically low, was satisfactory, especially taking into account the advanced tumor stage. The most common adverse events in the PRRT were hematological toxicity and renal failure. Despite studies demonstrate the efficacy and safety of PRRT with the radiotracer , this treatment modality is still considered under development.

Clinical value of 68Ga-DOTATATE PET/CT in pituitary adenoma: a pilot study / 中华核医学与分子影像杂志

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 SUV 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) cm3 vs (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 68 Ga-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.

Synthesis and in vivo evaluation of 68Ga-DOTATATE in mice / 中华核医学与分子影像杂志

Objective To synthesize 68 Ga-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 68GaDOTATATE 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 68 Ga-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.

Utilidad del PET/CT con análogos de somatostatina marcados con Ga68 en el diagnóstico de síndrome de Cushing secundario a tumor neuroendocrino pancreático / Pancreatic neuroendocrine tumor diagnosed with positron emission tomography/ct scan (PET/CT): report of one case

We report a 28 years old woman consulting for weight gain, progressive muscle weakness and appearance of facial plethora. Laboratory showed high cortisol and ACTH levels. Magnetic resonance of sella turcica was normal and an abdominal magnetic resonance showed a pancreatic mass, suggestive of a neuroendocrine tumor. A PET/CT with somatostatin analogues demonstrated an intense over-expression of somatostatin receptors in the tumor. The patient was subjected to a pancreatectomy and the day after surgery, ACTH levels decreased to less than 5 pg/ml. The patological study of the surgical piece showed a neuroendocrine carcinoma. The patient had a good postoperative evolution.

Tratamiento de tumores neuroendocrinos (TNE) con péptidos análogos de la somatostatina marcados con radionucleidos / Treatment of neuroendocrine tumors (NET) with radiolabelled somatostatin analogues

Propósito. Los TNE avanzados tienen escasa respuesta a radioterapia o quimioterapia, el tratamiento sistémico con análogos de la SST radiactivos es una herramienta promisoria en su tratamiento. Presentamos nuestra experiencia, pionera en Latinoamérica, utilizando análogos de SST marcados con 90Y ó 177Lu. Material. Evaluamos 40 pacientes (50.3 años, rango 12-74) con TNE confirmados histológicamente y sobre-expresión de receptores de SST demostrada mediante imágenes. SPECT (111In-DOTATOC) ó PET/CT (68Ga-DOTATATE). Se evaluó respuesta clínica, laboratorio, imágenes con 111In-DOTATATE, post-terapia con 90Y ó 177Lu, 68Ga-DOTATATE PET/CT o TAC. Resultados. Observamos progresión de enfermedad en 10 (25.0 por ciento), remisión parcial en 25 (62.5 por ciento), enfermedad estable en 3 (7.5 por ciento) y remisión completa en 2 (5.0 por ciento). Hubo escasa toxicidad sin deterioro renal significativo. Observamos reducción tumoral y mejoría de calidad de vida en la mayoría de los pacientes. Conclusión. La terapia con radiopéptidos es un procedimento seguro y efectivo en el tratamiento de TNE avanzados.

Purpose. Advanced NETs have little response to radiotherapy or chemotherapy, systemic treatment with radioactive SST analogous is a promissory tool in its treatment. We present our pioneering experience in Latin America using analogous of SST labeled either with 90Y or 177Lu. Materials. We evaluated 40 patients (50.3 years, range 12-74) with histological proved NET and SST receptors over-expression demonstrated by SPECT or PET/CT images with 111In-DOTATOC or 68Ga-DOTATATE. We evaluated clinical response, laboratory test, images with 111In-DOTATATE, 90Y, 177Lu, and 68Ga-DOTATATE PET/CT or CT. Results. We observed progression of disease in 10 (7,5 percent), partial remission in 25 (62,5 percent), stable disease in 3 (7,5 percent) and complete remission in 2 (5,0 percent). There was little toxicity without significant renal deterioration. We observed tumor mass reduction and improvement of quality of life in most of the patients. Conclusion. The therapy with radiopeptides is a safe and effective procedure in the treatment of advanced NET.

Treatment of advanced neuroendocrine tumors with ~(90)Y-DOTATATE / 中华核医学杂志

Objective To evaluate the effcacy and side effects of [~(90)Y-1,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid (DOTA)~0,Tyr3]octreotate (~(90)Y-DOTATATE) combined with lysine as a renal protective agent.Methods Twenty-five patients with advanced neuroendocrine tumors were confirmed as somatostatin receptor subtype-2 (SSTR2)-positive by somatostatin receptor scintigraphy (SRS).Each patient received 1-5 cycles of treatment and the interval between two cycles of treatment was 6-9 weeks.~(90)Y-DOTATATE was administered intravenously within 30 min.Lysine was injected before and after the administration of ~(90)Y-DOTATATE.After each treatment cycle.the side effects were assessed according to National Cancer Institute Grading Criteria(NCIGC).The etticacy was evaluated by the WHO criteria 8 weeks after the last treatment.Results Pattial remission was found in 1 patient (4%).minor response in 3 patients(12%),stable disease in 16 patients (64%)and tumor progression in 5 patients (20%).Two patients suffered from renal functional injuries and 3 patients developed leukocytopenia.Three patients showed nausea while another 3 patients presented vomiting.Conclusions ~(90)Y-DOTATATE in association with lysine may be a promising treatment method for the patients with metastatic and inoperable neuroendocrine tumors.More research work may be directed to reduce renal injury.

Una nueva modalidad diagnóstica para la detección de tumores neuroendocrinos con 68Ga-DOTATATE PET/CT: Caso clínico / Detection of neuroendocrine tumors by positron emission tomography-computed tomography with 68Ga-DOTATATE: Report of one case

We report a 74-year-old maie with liver metastases from a neuroendocrine tumor (NET) of unknown origin. Conventionai imaging studies with ultrasound, computed tomography coionoscopy and Positron emission tomography-computed tomography (PET/CT) with 18Flúor odeoxyglucose did not identify the site of orígin of the primary tumor. The patient was submitted for a PET/CT sean with a new radiopharmaceuticai, the somatostatin anaiogue 68Ga-DOTATATE. This new technique demostrated increased focal uptake at the ileocecal valve. This lesión and other two liver metastases were surgically removed. The histopathology and immunohistochemistry analysis confirmed the diagnosis of NET (carcinoid). This case illustrates the advantages of the PET/CT sean with 68Ga-DOTATATE.