Pharmacokinetic evaluation of [18F]PR04.MZ for PET/CT imaging and quantification of dopamine transporters in the human brain.

PURPOSE: Dopamine transporters (DAT) modulate pre-synaptic dopamine and physiological functions such as movement and reward. DAT also mirrors disease state in neurological disorders, rendering it an essential diagnostic target. [18F]PR04.MZ is a new PET imaging agent for DAT with an improved affinity and selectivity profile, for which we here describe the complete pharmacokinetic evaluation in healthy controls. METHODS: Thirty-two healthy subjects underwent T1-weighted MRI and dynamic PET scans for 180 min with arterial blood sampling (n = 5) or 90 min without blood sampling (n = 25) after injection of 197.6 ± 12.2 MBq [18F]PR04.MZ. Blood and plasma metabolite analysis were performed. MRI-based normalization of brain images, delineation of VOIs, and kinetic modeling was conducted to determine distribution volumes (Vt) and binding potentials (BPnd). The impact of scan duration was evaluated and repeated PET scans were performed to assess test-retest variability (n = 5). A static imaging protocol has been validated for clinical applications. RESULTS: [18F]PR04.MZ showed rapid metabolization in circulation, very high uptake in striatum and midbrain, and very low non-specific binding. The two-tissue compartment model 2TCM provided best fits for measured time-activity-curves and calculated Vts in putamen, caudate, substantia nigra pars compacta (SNpc), and cerebellar cortex were 11.83, 9.73, 2.12, and 0.57, respectively. All non-invasive models correlated well with BPnd values derived from 2TCM but underestimated DAT availability by about 28-33%. Of those, simplified reference tissue model (SRTM) provided the best fits, lowest Akaike Information Criteria values, and BPnd values of 14.82, 11.95, and 2.63 in putamen, caudate, and SNpc, respectively. BPnd estimates for striatal regions and SNpc were stable between 90 and 130 min post-injection. Test-retest results were excellent, showing low variability in all and excellent reliability in most relevant regions. Static imaging from 60 to 90-min post-injection is a viable alternative for quantification. CONCLUSIONS: [18F]PR04.MZ is a PET tracer with very high affinity, selectivity, and specific uptake in striatum and midbrain. 2TCM and SRTM provide good fits, high and stable Vts or BPnds, and good test-retest reliability for precise quantification of DAT in human subjects.

[18F]PR04.MZ PET/CT Imaging for Evaluation of Nigrostriatal Neuron Integrity in Patients With Parkinson Disease.

INTRODUCTION: Degeneration of dopaminergic, nigrostriatal neurons is the hallmark of Parkinson disease (PD), and PET quantification of dopamine transporters is a widely accepted method for differential diagnosis between idiopathic PD and essential tremor. [18F]PR04.MZ is a new PET tracer with excellent imaging properties allowing for precise quantification of striatal and extrastriatal dopamine transporter. Here we describe our initial experience with [18F]PR04.MZ PET/CT in a larger cohort of healthy controls and PD patients as a proof-of-concept study for this tracer. METHODS: Eighteen healthy subjects, 19 early PD patients (Hoehn-Yahr I-II), and 13 moderate-advanced PD patients (Hoehn-Yahr III-IV) underwent static PET/CT scans 60 to 90 minutes after injection of 5.16 ± 1.03 mCi (191 ± 38 MBq) [18F]PR04.MZ. Specific binding ratios (SBRs) were calculated for caudate nucleus, anterior putamen, posterior putamen, substantia nigra (SNpc), compared between different groups and correlated with clinical ratings. RESULTS: [18F]PR04.MZ showed very high and specific uptake in the putamen, caudate, and substantia nigra pars compacta and very low nonspecific binding in other brain regions, and SBR values for the control group were 22.3 ± 4.1, 19.1 ± 3.5, and 5.4 ± 1.2, respectively. A reduction of SBR values was observed in all regions and in both initial and moderate PD, ranging from 35% to 89% (P < 0.001). The observed pattern of reduction was posterior putamen > anterior putamen > substantia nigra pars compacta > caudate, with contralateral posterior putamen being the most affected region. Rostrocaudal depletion gradient was evident in all PD patients and progression correlated with motor manifestations. CONCLUSIONS: [18F]PR04.MZ PET/CT is a highly sensitive imaging modality for the detection of dopaminergic deficit in nigrostriatal pathways in PD.

The role of PET-CT in patients with incidental gallbladder cancer.

INTRODUCTION: After a cholecystectomy, incidental gallbladder cancer (IGC) requires accurate imaging studies to determine the actual extent of the disease to properly tailor subsequent treatment. The aim of this study was to evaluate the utility of (18)F-fluorodeoxyglucose positron emission tomography-computed tomography ((18)FDG PET-CT) to provide optimal pre-treatment staging in patients with IGC. MATERIAL AND METHODS: Between January 2006 and August 2008, all patients with IGC and at least muscular layer invasion were studied with (18)FDG PET-CT. The examination was considered positive when the standardized uptake values (SUV) were >/=2.5. In all instances patients were offered to undergo definitive exploration and possible radical resection. RESULTS: The series included 32 patients, 26 women and 6 men, with a median age of 57 years (range 30-81 years). The examination was performed at a median time of 6 weeks after cholecystectomy (range 2-52 weeks). (18)FDG PET-CT was negative in 13 patients and positive in 19 patients: 9 with localized potentially resectable disease (PRD) and in 10 with disseminated disease. Of the 13 patients with negative PET-CT, 9 refused surgery and 4 underwent formal exploration: 3 patients were resected with no disease identified in the final pathology report (FPR) and 1 was not resected as a result of peritoneal carcinomatosis. Of the 9 with PRD, 4 patients refused reoperation and 5 underwent exploration: 3 were resected with residual disease noted in the FPR and 2 did not undergo resection because of dissemination. Two patients with disseminated disease were reoperated and in both instances disseminated disease was confirmed. The median survival for the entire group was 20.3 months (range 1.6-32.9 months). The median survival for those patients with negative PET-CT was 13.5 months (range 5.6-32.9 months), 6.2 months (range 1.6-18.7 months) for localized potentially resectable disease and 4.9 months (range 2-14.1 months) for disseminated disease (P < 0.003). CONCLUSIONS: For patients presenting with stage T1b or greater IGC, the use of (18)FDG PET-CT will help reduce the number of patients undergoing non-therapeutic re-exploration and may help to determine the likely prognosis. (18)FDG PET-CT might be a useful tool for the selection of patients for potentially curative treatment.

Imaging Nigrostriatal Dopaminergic Deficit in Holmes Tremor with 18F-PR04.MZ-PET/CT.

Holmes tremor is an infrequent clinical syndrome characterized by unilateral rest, postural, and action tremor often secondary to a brain lesion. We herein report an interesting case of Holmes tremor studied with PET and F-PR04.MZ, a new high-affinity radioligand for dopamine transporters, currently under investigation at our center. F-PR04.MZ-PET can be useful to study the integrity of the nigrostriatal dopaminergic system to improve diagnosis and therapeutic outcome in patients with Holmes tremor and Parkinson disease.

Results of a Prospective Multicenter International Atomic Energy Agency Sentinel Node Trial on the Value of SPECT/CT Over Planar Imaging in Various Malignancies.

UNLABELLED: We aimed to assess the additional value of SPECT/CT over planar lymphoscintigraphy (PI) in sentinel node (SN) detection in malignancies with different lymphatic drainage such as breast cancer, melanoma, and pelvic tumors. METHODS: From 2010 to 2013, 1,508 patients were recruited in a multicenter study: 1,182 breast cancer, 262 melanoma, and 64 pelvic malignancies (prostate, cervix, penis, vulva). PI was followed by SPECT/CT 1-3 h after injection of (99m)Tc-colloid particles. Surgery was performed the same or next day. RESULTS: Significantly more SNs were detected by SPECT/CT for breast cancer (2,165 vs. 1,892), melanoma (602 vs. 532), and pelvic cancer (195 vs. 138), all P < 0.001. The drainage basin mismatch between PI and SPECT/CT was 16.5% for breast cancer, 11.1% for melanoma, and 51.6% for pelvic cancers. Surgical adjustment was 17% for breast cancer, 37% for melanoma, and 65.6% for pelvic cancer. CONCLUSION: SPECT/CT detected more SNs and changed the drainage territory, leading to surgical adjustments in a considerable number of patients in all malignancies studied but especially in the pelvic cancer group because of this group's deep lymphatic drainage. We recommend SPECT/CT in all breast cancer patients with no SN visualized on PI, all patients with melanoma of the head and neck or trunk, all patients with pelvic malignancies, and those breast cancer and melanoma patients with unexpected drainage on PI.

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

We report a 74-year-old male with liver metastases from a neuroendocrine tumor (NET) of unknown origin. Conventional imaging studies with ultrasound, computed tomography colonoscopy and Positron emission tomography-computed tomography (PET/CT) with 18Fluor odeoxyglucose did not identify the site of origin of the primary tumor. The patient was submitted for a PET/CT scan with a new radiopharmaceuticai, the somatostatin analogue 68Ga-DOTATATE. This new technique demonstrated increased focal uptake at the ileocecal valve. This lesion 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 scan with 68Ga-DOTATATE.

[Fibrolamellar liver carcinoma: report of two cases and review of the literature]. / Carcinoma hepatocelular variedad fibrolamelar metastásico en menores de 20 años: Reporte de 2 casos tratados con intención curativa y revisión de la literatura.

Fibrolamellar hepatocellular carcinoma (FLC) is a rare histologic variant of hepatocellular carcinoma that appears most commonly in teenagers and young adults. The diagnosis is often made incidentally and surgical resection is the only curative treatment. Here we report two cases of incidental FLC involving a 19 year-old male, initially diagnosed with screening abdominal ultrasound, and a 14 year-old female that presented with abdominal pain. Diagnostic workup consisted of abdominal PET/CT and MR1 Imaging studies and tissue diagnosis was confirmed with percutaneous liver biopsy. Both patients were treated with radical liver resection/tumor excision. However, tumor recurrence was observed in both during short-term follow-up. The male patient was treated successfully with surgical treatment however the female patient succumbed top regression of disease.

Thyroid metastases from gallbladder cancer.

BACKGROUND: Gallbladder cancer is an aggressive malignancy and radical resection is the only curative therapy available. Metastatic disease in the thyroid is rarely seen; however, different studies have confirmed that the most common primary tumor source is the kidney. CASE REPORT: Thyroid metastases from tumors originating in the gastrointestinal tract have been reported. We report a patient with gallbladder cancer (T2N1M0) treated with radical resection and postoperative chemoradiation who developed thyroid metastases.

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.

Carcinoma hepatocelular variedad fibrolamelar metastásico en menores de 20 años: Reporte de 2 casos tratados con intención curativa y revisión de la literatura / Fibrolamellar liver carcinoma: Report of two cases

Fibrolamellar hepatocellular carcinoma (FLC) is a rare histologic variant of hepatocellular carcinoma that appears most commonly in teenagers and young adults. The diagnosis is often made incidentally and surgical resection is the only curative treatment. Here we report two cases of incidental FLC involving a 19 year-old male, initially diagnosed with screening abdominal ultrasound, and a 14 year-old female that presented with abdominal pain. Diagnostic workup consisted of abdominal PET/CT and MRI Imaging studies and tissue diagnosis was confirmed with percutaneous liver biopsy. Both patients were treated with radical liver resection/tumor excision. However, tumor recurrence was observed in both during short-term follow-up. The male patient was treated successfully with surgical treatment however the female patient succumbed top regression of disease.

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.

Gallium-68 (68Ga); the revival of an old positron emission tomography (PET) agent: the leading experience in Chile

In January 2008, we set up a 68Ge/ 68Ga generator able to produce enough quantities of 68Ga to label the same polypeptides, somatostatin analogos, used to treat patients suffering from neuroendocrine tumors. As far as we know, this is the first time that such a device is installed in Latin-America for specific PET/CT imaging different from 18F. During the last three months we have studied 30 patients for staging, re-staging and treatment control of neuroendocrine tumors using PET/CT images with 68Ga-DOTATATE. In all cases the image quality was excellent, providing clinically useful information in most of them. 68Ga is a very promising positron emitter radionuclide, cyclotron-independent, to label peptides and other molecules that open a wide window for Molecular Imaging.

En Enero de 2008 instalamos un generador de 68Ge/ 68Ga capaz de producir cantidades suficientes de 68Ga para marcar los mismos péptidos, análogos de la somatostatina, utilizados para el tratamiento de pacientes con tumores neuroendocrinos. De acuerdo con nuestro conocimiento, esta es la primera vez que se utilizada este aparato en Latinoamérica para obtener imágenes PET/CT específicas con un agente diferente al 18F. Durante los últimos tres meses hemos estudiado 30 pacientes con tumores neuroendocrinos con 68Ga-DOTATATE para etapificación, re-etapificación y control de tratamiento mediante imágenes PET/CT. En todos los casos la calidad de la imagen fue excelente proporcionando información clínicamente útil en la mayoría de ellos. 68Ga es un promisorio radionucleido emisor de positrones, independiente de un ciclotrón, para marcar péptidos y otras moléculas abriendo una amplia ventana para las Imágenes Moleculares.

Linfocintigrafía en quilotórax: caso clínico / Lymphoscintigraphy in chylothorax: clinical case

Se presenta un caso de quilotórax de aparición espontánea en una niña de 13 años, sus manifestaciones clínicas, exámenes de laboratorio e imágenes que contribuyeron al diagnóstico, con énfasis en el uso de la linfocintigrafía que permitió detectar el sitio de la filtración de quilo hacia la cavidad pleural y que fue posteriormente confirmado y exitosamente reparado quirúrgicamente

Radionuclide evaluation of enterogastric reflux using caerulein to stimulate biliary excretion

O refluxo biliar desempenha um importante papel na patogenia da esofagite, gastrite e úlcera gástrica. Recentemente, um método utilizando radioisótopos tem sido empregado como o mais fisiológico na avaliaçäo desta condiçäo. No presente artigo, estudou-se o refluxo enterogástrico, empregando o Tc-99m DISIDA em 37 pacientes em várias situaçöes, a saber: esofagite de refluxo, úlcera péptica, ressecçöes gástricas, vagotomia gástrica proximal e colecistite crônica calculosa. Em 19 pacientes, o esvaziamento vesicular foi estimulado com uma dieta hipercalórica altamente concentrada e nos restantes com a injeçäo endovenosa de 5 ng/kg (14 casos) ou 50 ng/kg de ceruleína. Os resultados obtidos sugerem que a injeçäo endovenosa de ceruleína nas doses de 5 ou 50 ng/kg está associada com refluxo enterogástrico significativo

Spect cerebral en jaqueca acompañada: presentación de 3 casos clínicos / Brain spect in migraine accompagnee: presentation of 3 clinical cases

Se presentan 3 casos clínicos de jaqueca acompañada, en quienes se pudo demostrar una reducción transitoria del flujo sanguíneo cerebral regional mediante un SPECT con 99mTc-HMPAO cerebral inyectado durante la fase aguda. En dos de ellos el SPECT de control de 24 horas demostró regresión de las alteraciones de perfusión