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.
18
FPR04.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
18
FPR04.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 (V
t
) and binding potentials (BP
nd
). 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
18
FPR04.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 V
t
s 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 BP
nd
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 BP
nd
values of 14.82, 11.95, and 2.63 in putamen, caudate, and SNpc, respectively. BP
nd
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
18
FPR04.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 V
t
s or BP
nd
s, and good test-retest reliability for precise quantification of DAT in human subjects.
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.
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.
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.
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.
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. 18FPR04.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 18FPR04.MZ PET/CT in a larger cohort of healthy controls and PD patients as a proof-of-concept study for this tracer.
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) 18FPR04.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.
18FPR04.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.
18FPR04.MZ PET/CT is a highly sensitive imaging modality for the detection of dopaminergic deficit in nigrostriatal pathways in PD.
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.
Se presenta un caso clínico de paciente con linfoma no Hodgkin tratado; en control tomográfico habitual se le solicitó PET-CT para complementar su estudio, que demuestra un foco metabólicamente ...activo en el espesor de músculo aductor izquierdo sin traducción tomográfica evidente. La lesión fue estudiada con ultrasonografia de partes blandas y biopsia dirigida, que resultó positiva para infiltración secundaria por linfoma. Este caso demuestra la utilidad de las técnicas complementarias en el manejo de estos pacientes, en especial la utilidad del PET-CT en el estudio de sitios inhabituales de diseminación. En este examen existe la posibilidad de identificar con precisión la localización de las lesiones mediante la TC complementaria, lo que permite efectuar posteriormente el estudio dirigido.
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 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG PET-CT) to provide optimal pre-treatment staging in patients with IGC.
Between January 2006 and August 2008, all patients with IGC and at least muscular layer invasion were studied with 18FDG 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.
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). 18FDG 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).
For patients presenting with stage T1b or greater IGC, the use of 18FDG PET-CT will help reduce the number of patients undergoing non-therapeutic re-exploration and may help to determine the likely prognosis. 18FDG PET-CT might be a useful tool for the selection of patients for potentially curative treatment.
Thyroid Metastases from Gallbladder Cancer Butte, Jean M.; Marín, Luis; Meneses, Manuel ...
Journal of gastrointestinal surgery,
07/2009, Volume:
13, Issue:
7
Journal Article
Peer reviewed
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.