Dirk Heute

68Ga-DOTA-Tyr3-Octreotide PET in Neuroendocrine Tumors: Comparison with Somatostatin Receptor Scintigraphy and CT

The aim of this study was to evaluate the diagnostic value of a new somatostatin analog, 68Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N′,N″,N″′-tetraacetic acid-d-Phe1-Tyr3-octreotide (68Ga-DOTA-TOC), for PET in patients with known or suspected neuroendocrine tumors. PET was compared with conventional scintigraphy and dedicated CT. Methods: Eighty-four patients (48 men, 36 women; age range, 28–79 y; mean age ± SD, 58.2 ± 12.2 y) were prospectively studied. For analysis, patients were divided into 3 groups: detection of unknown primary tumor in the presence of clinical or biochemical suspicion of neuroendocrine malignancy (n = 13 patients), initial tumor staging (n = 36 patients), and follow-up after therapy (n = 35 patients). Each patient received 100–150 MBq 68Ga-DOTA-TOC. Imaging results of PET were compared with 99mTc-labeled hydrazinonicotinyl-Tyr3-octreotide (99mTc-HYNIC-TOC) and 111In-DOTA-TOC. CT was also performed on every patient using a multidetector scanner. Each imaging modality was interpreted separately by observers who were unaware of imaging findings before comparison with PET. The gold standard for defining true-positive (TP), true-negative (TN), false-positive (FP), and false-negative (FN) results was based on all available histologic, imaging, and follow-up findings. Results: PET was TP in 69 patients, TN in 12 patients, FP in 1 patient, and FN in 2 patients, indicating a sensitivity of 97%, a specificity of 92%, and an accuracy of 96%. The FP finding was caused by enhanced tracer accumulation in the pancreatic head, and the FN results were obtained in patients with a tumor of the gastrointestinal tract displaying liver metastases. 68Ga-DOTA-TOC showed higher diagnostic efficacy compared with SPECT (TP in 37 patients, TN in 12 patients, FP in 1 patient, and FN in 34 patients) and diagnostic CT (TP in 41 patients, TN in 12 patients, FP in 5 patients, and FN in 26 patients). This difference was of statistical significance (P < 0.001). However, the combined use of PET and CT showed the highest overall accuracy. Conclusion: 68Ga-DOTA-TOC PET shows a significantly higher detection rate compared with conventional somatostatin receptor scintigraphy and diagnostic CT with clinical impact in a considerable number of patients.

Diffusion weighted imaging best discriminates PD from MSA-P : A comparison with tilt table testing and heart MIBG scintigraphy

Both diffusion weighted magnetic resonance imaging (DWI) of the basal ganglia and meta‐iodobenzylguanidin (MIBG) scintigraphy of the heart have been reported useful in the differential diagnosis of patients with Parkinsons disease (PD) vs. the parkinson variant of multiple system atrophy (MSA‐P). Their diagnostic value, however, has never been directly compared in patients with parkinsonism and autonomic dysfunction. We have studied 9 patients with PD and 9 patients with MSA‐P matched for age and disease severity. Regional trace of the diffusion tensor values were determined in the putamina. Cardiac MIBG uptake was quantified by comparing regions of interest over heart and mediastinum Heart/Mediastinum (H/M) ratio. Furthermore, all patients underwent tilt testing. PD patients showed significantly lower H/M ratios than normal controls; however, there was considerable overlap between the two patient groups. We did not detect any significant differences of blood pressure response to passive tilt between the two patient groups. Sensitivity of MIBG scintigraphy versus DWI for the differentiation of MSA‐P from PD was 55.6% vs. 100%, specificity 88.8% vs. 100%, and area under the curve 0.802 vs. 1.000. Our data suggest that DWI is superior to both tilt table testing and MIBG scintigraphy in the differential diagnosis of PD versus MSA‐P.

Response of Recurrent High-Grade Glioma to Treatment with 90Y-DOTATOC

The treatment of patients with high-grade malignant glioma still represents an unsolved clinical problem. We report the treatment of 3 patients who had World Health Organization grade IV recurrent glioblastoma: a 23-y-old woman and 2 men aged 61 and 62 y. Methods: All 3 patients were treated with the somatostatin receptor radiopharmaceutical 90Y-labeled [1,4,7,10-tetraazacyclododecane-N,N′,N″,N″′-tetraacetic acid0-d-Phe1,Tyr3]octreotide (DOTATOC). A cumulated dose of 1.7–2.2 GBq given in 3 or 4 cycles was locally injected into a previously implanted catheter system. Results: Treatment was successful in all 3 patients, with only minor side effects reported. After treatment, MRI and PET showed complete remission in one patient and partial remission in the other patients. These findings correlated well with clinical improvement and improved quality of life. Conclusion: Receptor-mediated radionuclide therapy by locally injected 90Y-DOTATOC is feasible and well tolerated. This approach represents an attractive strategy for the treatment of locally recurring or progressing glioblastoma.

Concordance between results of somatostatin receptor scintigraphy with 111In-DOTA-DPhe1-Tyr3-octreotide and chromogranin A assay in patients with neuroendocrine tumours

PurposeSomatostatin receptor scintigraphy (SRS) and chromogranin A (CgA) assay have successfully been implemented in the clinical work-up and management of neuroendocrine tumour (NET) patients. However, there is still a lack of studies comparing results in these patients. Our aim was to compare directly in NET patients SRS and CgA assay results with special regard to tumour features such as grade of malignancy, primary origin, disease extent and function.MethodsOne hundred twenty consecutive patients with histological confirmed NETs were investigated with 111In-DOTA-DPhe1-Tyr3-octreotide (111In-DOTA-TOC) SRS and CgA immunoradiometric assay. Tumours were classified by cell characteristics [well-differentiated NETs, well-differentiated neuroendocrine carcinomas, poorly differentiated neuroendocrine carcinomas (PDNECs)], primary origin (foregut, midgut, hindgut, undetermined), disease extent (limited disease, metastases, primary tumour and metastases) and functionality (secretory, nonsecretory).ResultsSRS was positive in 107 (89%) patients; CgA levels were increased in 95 (79%) patients. Overall, concordance between SRS and CgA results was found in 84 patients. Positive SRS but normal CgA level were found in 24 patients, with higher prevalence (p < 0.05) in patients with nonsecretory tumours. Conversely, negative SRS but CgA level increased were seen in 12 patients, with higher proportion (p < 0.05) in patients with PDNECs and tumours of hindgut origin.ConclusionsOverall, 111In-DOTA-TOC SRS proved to be more sensitive than CgA in NETs patients. Tumour differentiation, disease extent and presence of liver metastases impact both SRS and CgA results, whereas nonsecretory activity is a negative predictor of only CgA increase. PDNECs and hindgut origin of tumours predispose to discrepancies with negative SRS but increased CgA levels.

Optimized Conformal Paraaortic Lymph Node Irradiation is not Associated with Enhanced Renal Toxicity

Background and Purpose:For patients with gynecologic carcinomas, irradiation of paraaortic lymph nodes (PLNs) is a routine treatment concept. Planning target volumes (PTVs) individually optimized by radiation field delineations along the big vessels permit the inclusion of at least 97% of potentially involved PLNs. However, this novel treatment technique might increase radiation-induced nephrotoxicity. Therefore, the actual incidence of kidney damage after PLN irradiation has to be assessed in order to validate the safety of this treatment concept.Patients and Methods:19 patients were treated with irradiation alone (50.4 Gy; 5 × 1.8 Gy/week) and monitored for up to 90 months. Functional renal parameters, namely renal plasma flow (RPF) and glomerular filtration rate (GFR), were assessed by dynamic renal scintigraphy. Additionally, patients were clinically observed (i.e., hypertension, proteinuria) and calculations of normal-tissue complication probability (NTCP) values for nonuniform kidney irradiation were performed using the Lyman-Wolbarst algorithm.Results:Two patients with anticipated moderate NTCP values (12.6% and 8.7%) showed slightly impaired RPF rates at 12, 24, and after 48 months of follow-up. Only one patient in the subgroup showing NTCP values > 50% (n = 9) developed a notable impairment of renal RPF. However, all patients including those with elevated complication probabilities exhibited neither impaired GFR nor clinically apparent symptoms related to a loss of functioning renal tissue from 12 to > 48 months post irradiation.Conclusion:Conformal irradiation of retroperitoneal lymph nodes with individual PTV delineation appears not to be associated with clinically relevant functional impairment of the kidneys.Hintergrund und Ziel:Die Behandlung von Patientinnen mit gynäkologischen Tumoren beinhaltet häufig die Bestrahlung der paraaortalen Lymphknoten (PLNs). Durch eine individuelle Anpassung des Planungszielvolumens (PTV) an den Verlauf der großen abdominalen Gefäße können mindestens 97% aller potentiell befallenen PLNs behandelt werden. Die dadurch z.T. vergrößerten PTVs könnten aber mit einer gesteigerten Inzidenz für eine radiogene Nephropathie einhergehen. Um die Sicherheit dieser neuen Bestrahlungstechnik zu überprüfen, wurde das tatsächliche Auftreten von radiogenen Nephropathien nach solchen PLN-Bestrahlungen untersucht.Patienten und Methodik:19 Patientinnen mit gynäkologischen Tumoren, die eine Bestrahlung der PLNs (50,4 Gy; 5 × 1,8 Gy/Woche) ohne Chemotherapie in der Klinik der Autoren erhielten, wurden bis zu 90 Monate nachbeobachtet. Mittels seitengetrennter Nierenclearence wurden renaler Plasmafluss (RPF) und glomeruläre Filtrationsrate (GFR) bestimmt und die Patientinnen regelmäßig klinisch untersucht (u.a. Blutdruck, Proteinurie). Außerdem wurden für jede Patientin aus den dreidimensionalen Bestrahlungsplänen für beide Nieren NTCP-Werte (Wahrscheinlichkeit von Normalgewebskomplikationen) nach dem Lyman-Wolbarst-Algorithmus berechnet.Ergebnisse:Zwei Patientinnen mit moderaten NTCP-Werten (12,6% und 8,7%) wiesen nach 12, 24 und 48 Monaten eine leichte Störung des RPF auf. Nur eine Patientin aus der Gruppe mit NTCP-Werten > 50% (n = 9) entwickelte eine ausgeprägtere Störung des RPF. Keine Patientin zeigte eine Störung der GFR oder klinische Symptome einer Nierenschädigung in der Zeit von 12 bis > 48 Monate nach der Bestrahlung.Schlussfolgerung:Die konformale Bestrahlung der PLNs mit einem individuellen, dem Verlauf der großen Gefäße angepassten PTV führte im eigenen Patientenkollektiv in keinem Fall zu einer klinisch relevanten radiogenen Nephropathie.