Sabine Haufe

MR to assess renal function in children

Abstract.Renal function evaluation in the pediatric patient is generally based on scintigraphic examinations where a baseline gamma-camera renography is used to determine single kidney function, and diuresis renography is obtained to assess urinary drainage from the pelvicalyceal system. Magnetic resonance imaging also permits the evaluation of renal functional processes using fast dynamic sequences. Principally, an agent cleared by renal excretion is intravenously injected and its cortical uptake, parenchymal transport, and eventually its urinary excretion are followed with serial images. Different approaches have been presented most of which are based on T1-weighted gradient-recalled echo sequences with short TR and TE and a low flip angle obtained after intravenous injection of Gd-DTPA or Gd-DOTA. These techniques permit renal functional assessment using different qualitative and quantitative parameters; however, most of these methods are not suitable for the evaluation of urinary tract dilatation in infants and children. For the diagnostic work-up of children with congenital urinary tract obstruction and malformation a technique was developed which permits quantitative determination of single kidney function, in addition to evaluating urinary excretion disturbances analogous to that possible with scintigraphy.

Hepatic arterial infusion enhances DOTATOC radiopeptide therapy in patients with neuroendocrine liver metastases.

Intravenously administered radiolabeled peptides targeting somatostatin receptors are used for the treatment of unresectable gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Recently, we demonstrated a high first-pass effect during intra-arterial (i.a.) administration of positron emission tomography (PET) labeled (68)Ga-DOTA(0)-d-Phe(1)-Tyr(3)-octreotide (DOTATOC). In this pilot study, we investigated the therapeutic effectiveness of arterial administered DOTATOC, labeled with the therapeutic β emitters (90)Y and (177)Lu. (90)Y- and/or (177)Lu-DOTATOC were infused into the hepatic artery of 15 patients with liver metastases arising from GEP-NETs. Response was assessed using DOTATOC-PET, multiphase contrast enhanced computed tomography, magnetic resonance imaging, and the serum tumor marker chromogranin A. Pharmacokinetic data of the arterial approach were assessed using (111)In-DOTATOC scans. With the treatment regime of this pilot study, complete remission was achieved in one (7%) patient and partial remission was observed in eight (53%) patients, six patients were classified as stable (40%; response evaluation criteria in solid tumors criteria). The concomitant decrease of elevated serum tumor marker confirmed the radiologic response. Median time to progression was not reached within a mean follow-up period of 20 months. Receptor saturation and redistribution effects were identified as limiting factors for i.a. DOTATOC therapy. The high rate of objective radiologic response in NET patients treated with arterial infusion of (90)Y-/(177)Lu-DOTATOC compares favorably with systemic chemotherapy and intravenous radiopeptide therapy. While i.a. DOTATOC therapy is only applicable to patients with tumors of limited anatomic distribution, the results of this pilot study are a promising development in the treatment of GEP-NET and warrants further investigation of this novel approach.

Functional diagnosis of residual lymphomas after radiochemotherapy with positron emission tomography comparing FDG- and FLT-PET

Positron emission tomography (PET) using 2-deoxy-2-[18F]fluoro-d-glucose (FDG) is used as a functional imaging technique for the staging and follow-up of lymphomas. However, additional information about the tumor proliferation rate using 3′-deoxy-3′-[18F]fluorothymidine (FLT) may be useful for the assessment of prognosis. We enrolled 48 patients with Hodgkins (n = 15) and non-Hodgkins lymphoma (n = 33) with residual masses >2 cm examined by tracer studies with FDG and FLT. The results were related to median overall and progression-free survival. In 15 out of 48 patients analysed using FDG, positive results were found. Using FLT, 10 out of 48 patients were positive. 33 patients were FDG negative. Eight patients were positive both using FDG and FLT. Overall survival for patients with a negative PET scan was significantly higher than for patients with positive PET, irrespective of the tracer used. FLT alone was able to discriminate between patients with long or short overall survival. However, there was no statistical significance comparing FDG/FLT negative versus FDG negative alone. Although FDG detected more lesions than did FLT, the additional biological characterization of tumor tissue with respect to proliferation by FLT might be useful by providing complementary information for the identification of recurrence. However, the present data show no advantage of combined FDG/FLT studies over FDG alone with respect to the prediction of survival.

Skeletal scintigraphy indicates disease severity of cardiac involvement in patients with senile systemic amyloidosis

BACKGROUND Senile systemic amyloidosis (SSA) is a common aging phenomenon in the elderly population. Nevertheless, pre-mortem diagnosis of SSA is rare. Thus, data on clinical characterization and disease severity are limited. METHODS 36 consecutive SSA patients (71.6 [64.7-82.7]years) were evaluated by electrocardiography, echocardiography, laboratory tests, and (99m)Technetium-3,3-diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) scintigraphy (n=20). RESULTS In addition to cardiac involvement, amyloid deposition was found in rectum (n=6), peripheral nerves (n=2), and urinary bladder (n=2). Five patients showed low voltage pattern. Thickness of interventricular septum (IVS) was 20 [12-27]mm. LV longitudinal function was diminished (TDI-s 5 [3-11] cm/s; MAPSE 6.5 [2.5-19]mm; TAPSE 12.5 [2-24]mm). LV systolic function (LV-EF<45%) was markedly decreased in 19 patients. Plasma levels of troponin T (0.05 [0.01-0.23]µg/L) and NT-proBNP (4318 [205-16597]ng/L) were elevated. (99m)Tc-DPD heart retention was 7.8 [2.4-11.0]% and correlated with MAPSE (ρ=-0.716; p=0.0018), TAPSE (ρ=-0.491; p<0.05), and IVS (ρ=0.556; p=0.0153). Heart-to-body ratio correlated with MAPSE (ρ=-0.771; p=0.0018), IVS (ρ=0.603; p=0.0086). Twelve patients died during follow-up of 27.4 [0.1-106.2]months. Exclusively (99m)Tc-DPD heart retention, diastolic dysfunction and in trend MAPSE were associated with patients outcome. Interestingly, risk predictors that were well established in patients with AL amyloidosis were not predictive for survival in patients with SSA. CONCLUSIONS This study gave first evidence that (99m)Tc-DPD HR may be capable to display the extent of cardiac amyloid deposition. Moreover, this study suggested that (99m)Tc-DPD HR, diastolic dysfunction and in trend MAPSE are associated with poor outcome. Nevertheless, these findings need to be established in a larger prospective trial.

Non-randomized therapy trial to determine the safety and efficacy of heavy ion radiotherapy in patients with non-resectable osteosarcoma

BackgroundOsteosarcoma is the most common primary malignant bone tumor in children and adolescents. For effective treatment, local control of the tumor is absolutely critical, because the chances of long term survival are <10% and might effectively approach zero if a complete surgical resection of the tumor is not possible. Up to date there is no curative treatment protocol for patients with non-resectable osteosarcomas, who are excluded from current osteosarcoma trials, e.g. EURAMOS1. Local photon radiotherapy has previously been used in small series and in an uncontrolled, highly individualized fashion, which, however, documented that high dose radiotherapy can, in principle, be used to achieve local control. Generally the radiation dose that is necessary for a curative approach can hardly be achieved with conventional photon radiotherapy in patients with non-resectable tumors that are usually located near radiosensitive critical organs such as the brain, the spine or the pelvis. In these cases particle Radiotherapy (proton therapy (PT)/heavy ion therapy (HIT) may offer a promising new alternative. Moreover, compared with photons, heavy ion beams provide a higher physical selectivity because of their finite depth coverage in tissue. They achieve a higher relative biological effectiveness. Phase I/II dose escalation studies of HIT in adults with non-resectable bone and soft tissue sarcomas have already shown favorable results.Methods/DesignThis is a monocenter, single-arm study for patients ≥ 6 years of age with non-resectable osteosarcoma. Desired target dose is 60-66 Cobalt Gray Equivalent (Gy E) with 45 Gy PT (proton therapy) and a carbon ion boost of 15-21 GyE. Weekly fractionation of 5-6 × 3 Gy E is used. PT/HIT will be administered exclusively at the Ion Radiotherapy Center in Heidelberg. Furthermore, FDG-PET imaging characteristics of non-resectable osteosarcoma before and after PT/HIT will be investigated prospectively. Systemic disease before and after PT/HIT is targeted by standard chemotherapy protocols and is not part of this trial.DiscussionThe primary objectives of this trial are the determination of feasibility and toxicity of HIT. Secondary objectives are tumor response, disease free survival and overall survival. The aim is to improve outcome for patients with non-resectable osteosarcoma.Trail RegistrationRegistration number (ClinicalTrials.gov): NCT01005043

Nuclear Medicine Procedures for the Diagnosis of Acute and Chronic Renal Failure

The focus of this review is on the current role of nuclear imaging studies in the clinical evaluation of patients with acute and chronic renal failure. In this setting nuclear imaging has two roles: diagnostic and prognostic, indicating that these methods are an essential component in the evaluation of renal diseases. The functional assessment of the kidney by nuclear medicine procedures is based on the use of radioisotopes bound to non-metabolized molecules with known pharmacokinetics. Renal scintigraphy is usually applied for the assessment of renal function expressed as glomerular filtration rate, effective renal plasma flow or more generally kidney perfusion. Newer methods rely on positron emission tomography, which allows the generation of images with higher resolution and absolute quantitation of biological processes such as transport activities, enzyme activities or angiotensin receptors.

Detection and prognostic relevance of cytokeratin 20 in differentiated and anaplastic thyroid carcinomas by RT-PCR

BACKGROUND Metastatic disease in epithelial cancer results from tumor cell dissemination. We investigated an expression of cytokeratin 20 (CK20) by reverse transcriptase-polymerase chain reaction (RT-PCR) in differentiated (DTC) and anaplastic thyroid carcinomas (ATC) and correlated the results with TNM categories and the clinical follow-up. METHODS Tissue and blood samples of 32 patients with papillary (PTC), 17 patients with follicular (FTC), and 7 patients with ATC were obtained during operation and subjected to CK20 RT-PCR. RESULTS An expression of CK20 transcripts was detected in 47% of the tissue samples of PTC, 71% of the FTC, and 14% of the ATC. Patients with CK20-positive FTC had a significantly better outcome than patients with CK20-negative FTCs (P=.0016). Disseminated tumor cells were found in 9 of 22 (41%) blood samples of patients with CK20-positive carcinomas. The detection of CK20 transcripts in peripheral blood correlated with tumor categories. Four of 8 (50%) patients with DTC and circulating tumor cells developed local or distant recurrence compared with 3 of 13 (23%) patients with CK20-positive carcinomas and CK20-negative blood samples. CONCLUSION Our results suggest that CK20 might be a suitable differentiation marker in thyroid carcinomas. In patients with CK20-positive tumors, those with CK20-positive blood samples had a poorer prognosis. We suggest that patients with thyroid cancer with positive CK20 blood samples should be evaluated for further adjuvant therapies after surgery.

Afferent–efferent vessel dysfunction appears to be a specific characteristic of a large subset of patients with essential hypertension

Exercise renography makes it possible to subdivide essential hypertensives (EHs) into two distinct populations. Fifty to 60% develop exercise-mediated renal dysfunction and a transitory, severe reduction of glomerular filtration. The other subset of EHs does not have exercise-mediated renal dysfunction. We hoped to learn whether the disturbance is also present while EHs rest. Twenty-six EHs and 21 normotensive controls were studied with a resting sequential renogram using Tc-99m-mercaptoacetyl-triglycine (MAG3), a tracer excreted primarily by proximal tubular cells. EHs also had an exercise renogram. All persons had three consecutive 10-min dual-tracer infusion clearance determinations with 111In-DTPA and 131I-hippurate, for the simultaneous determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). To demonstrate the accuracy of the clearance procedure we sought to reproduce Hollenbergs results which show greater flow variability in EH than in normotension. Following this, the variability (VAR) of the GFR and ERPF as well as the variability fraction (VF), the ratio of GFR variability divided into the ERPF variability, were calculated. Hollenbergs results were reproduced. Sixteen of 26 essential hypertensives developed exercise-mediated renal dysfunction. GFR-VAR in EH differed from controls. The VF suggests that EHs with a bilateral abnormal exercise renogram have a more pronounced GFR variability than those EH with a normal exercise renogram. The results point to intraglomerular pressure fluctuations in patients with EH, and the VF suggests that this may be more pronounced in EHs with a bilateral abnormal exercise renogram than in those with a normal exercise renogram. It is hypothesized that the variable GFR provokes renin secretion in EH.

Erratum to: Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients (European Journal of Nuclear Medicine and Molecular Imaging, 10.1007/s00259-017-3711-7)

The article Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients, written by Ali AfsharOromieh et al., was originally published Online First without open access. After publication in volume 44, issue 8, page 1258–1268 the author decided to opt for Open Choice and to make the article an open access publication. Therefore, the copyright of the article has been changed to

[18F]PSMA-1007 PET Improves the Diagnosis of Local Recurrence and Lymph Node Metastases in a Prostate Cancer Patient With a History of Bilateral Hip Arthroplasty

A number of novel prostate-specific membrane antigen tracers have recently been introduced for positron emission tomography imaging of prostate cancer. This case report highlights a case of a patient with biochemical recurrence and a history of bilateral hip arthroplasty. Diagnostic certainty of conventional morphological imaging modalities such as computed tomography and magnetic resonance imaging is limited compared with positron emission tomography in these patients owing to artifacts.