Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in neuroendocrine tumours.

PURPOSE: Somatostatin-based radiopeptide treatment is generally performed using the ß-emitting radionuclides (90)Y or (177)Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. METHODS: In a comparative cohort study, patients with advanced neuroendocrine tumours underwent repeated cycles of [(90)Y-DOTA]-TOC or [(177)Lu-DOTA]-TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were employed to examine predictors of survival and adverse events for both treatment groups. RESULTS: Overall, 910 patients underwent 1,804 cycles of [(90)Y-DOTA]-TOC and 141 patients underwent 259 cycles of [(177)Lu-DOTA]-TOC. The median survival after [(177)Lu-DOTA]-TOC and after [(90)Y-DOTA]-TOC was comparable (45.5 months versus 35.9 months, hazard ratio 0.91, 95% confidence interval 0.63-1.30, p = 0.49). Subgroup analyses revealed a significantly longer survival for [(177)Lu-DOTA]-TOC over [(90)Y-DOTA]-TOC in patients with low tumour uptake, solitary lesions and extra-hepatic lesions. The rate of severe transient haematotoxicities was lower after [(177)Lu-DOTA]-TOC treatment (1.4 vs 10.1%, p = 0.001), while the rate of severe permanent renal toxicities was similar in both treatment groups (9.2 vs 7.8%, p = 0.32). CONCLUSION: The present results revealed no difference in median overall survival after [(177)Lu-DOTA]-TOC and [(90)Y-DOTA]-TOC. Furthermore, [(177)Lu-DOTA]-TOC was less haematotoxic than [(90)Y-DOTA]-TOC.

Targeted alpha-radionuclide therapy of functionally critically located gliomas with 213Bi-DOTA-[Thi8,Met(O2)11]-substance P: a pilot trial.

PURPOSE: Functionally critically located gliomas represent a challenging subgroup of intrinsic brain neoplasms. Standard therapeutic recommendations often cannot be applied, because radical treatment and preservation of neurological function are contrary goals. The successful targeting of gliomas with locally injected beta radiation-emitting (90)Y-DOTAGA-substance P has been shown previously. However, in critically located tumours, the mean tissue range of 5 mm of (90)Y may seriously damage adjacent brain areas. In contrast, the alpha radiation-emitting radionuclide (213)Bi with a mean tissue range of 81 microm may have a more favourable toxicity profile. Therefore, we evaluated locally injected (213)Bi-DOTA-substance P in patients with critically located gliomas as the primary therapeutic modality. METHODS: In a pilot study, we included five patients with critically located gliomas (WHO grades II-IV). After diagnosis by biopsy, (213)Bi-DOTA-substance P was locally injected, followed by serial SPECT/CT and MR imaging and blood sampling. Besides feasibility and toxicity, the functional outcome was evaluated. RESULTS: Targeted radiopeptide therapy using (213)Bi-DOTA-substance P was feasible and tolerated without additional neurological deficit. No local or systemic toxicity was observed. (213)Bi-DOTA-substance P showed high retention at the target site. MR imaging was suggestive of radiation-induced necrosis and demarcation of the tumours, which was validated by subsequent resection. CONCLUSION: This study provides proof of concept that targeted local radiotherapy using (213)Bi-DOTA-substance P is feasible and may represent an innovative and effective treatment for critically located gliomas. Primarily non-operable gliomas may become resectable with this treatment, thereby possibly improving the prognosis.

SPECT-CT imaging in degenerative joint disease of the foot and ankle.

The precise localisation of osteoarthritic changes is crucial for selective surgical treatment. Single photon-emission CT-CT (SPECT-CT) combines both morphological and biological information. We hypothesised that SPECT-CT increased the intra- and interobserver reliability to localise increased uptake compared with traditional evaluation of CT and bone scanning together. We evaluated 20 consecutive patients with pain of uncertain origin in the foot and ankle by radiography and SPECT-CT, available as fused SPECT-CT, and by separate bone scanning and CT. Five observers assessed the presence or absence of arthritis. The images were blinded and randomly ordered. They were evaluated twice at an interval of six weeks. Kappa and multirater kappa values were calculated. The mean intraobserver reliability for SPECT-CT was excellent (kappa = 0.86; 95% CI 0.81 to 0.88) and significantly higher than that for CT and bone scanning together. SPECT-CT had significantly higher interobserver agreement, especially when evaluating the naviculocuneiform and tarsometatarsal joints. SPECT-CT is useful in localising active arthritis especially in areas where the number and configuration of joints are complex.

Impact of concomitant thyroid pathology on preoperative workup for primary hyperparathyroidism.

BACKGROUND: The former standard surgical treatment in patients with primary hyperparathyroidism (pHPT) has been bilateral cervical exploration. New localization techniques and the possibility of intraoperative measurement of intact parathormone (iPTH) permit a focused, minimally invasive parathyroidectomy (MIP). The introduction of MIP without complete neck exploration leads to the potential risk of missing thyroid pathology. The aim of the present study is to evaluate the value of MIP in respect to coexisting thyroid findings and their impact on preoperative workup for primary hyperparathyroidism. METHODS: This is a prospective study including 30 consecutive patients with pHPT (median age 65 years; 17 females, 13 males). In all patients preoperative localization was performed by ultrasonography and 99m Tc-MIBI scintigraphy- Intraoperative iPTH monitoring was routinely done. RESULTS: Ten patients (33%) had a concurrent thyroid finding requiring additional thyroid surgery, and two patients (7%) with negative localization results underwent bilateral neck exploration. Therefore, MIP was attempted in 18 (60%) patients. The conversion rate to a four gland exploration was 6% (1/18). The sensitivities of 99m Tc-MIBI scanning and ultrasonography were 83.3% and 76.6%, respectively. The respective accuracy rates were 83.3% and 76.6%. Of note, the combination of the two modalities did not improve the sensitivity and accuracy in our patient population. During a median follow-up of 40 months, none of the patients developed persistent or recurrent hypocalcaemia, resulting in a 100% cure rate. CONCLUSION: Coexisting thyroid pathology is relatively frequent in patients with pHPT in our region. Among patients having pHPT without any thyroid pathology, the adenoma localization is correct with either ultrasonography or 99m Tc-MIBI scintigraphy in the majority of cases. MIP with iPTH monitoring are highly successful in this group of patients and this operative technique should be the method of choice.

[Stress-related vertical double vision and ptosis]. / Belastungsabhängige vertikale Doppelbilder und Ptosis. Diagnose: Okuläre Pseudomyasthenie bei Keilbeinmeningeom am Sinus cavernosus links.

A 43-year-old patient presented to our department because her left eyelid had exhibited drooping to varying extents for 2-3 months. Furthermore, in extreme positions or after rapid eye movement, she perceived diplopic images and was sensitive to light. The diagnosis of sphenoid meningioma was reached. Subsequently two rounds of radiopeptide therapy with (90)Y-DOTATOC (somatostatin analog) were administered within 3 months. This treatment approach led to a reduction of tumor volume in our patient as well as clinical improvement followed by stabilization.

Different strategies to overcome the effect of carbimazole on high- and low-dose radioiodine therapy: results from continuous dose-effect models.

BACKGROUND: Until now, it remains elusive which strategy - antithyroid drug withdrawal or increased radioiodine target doses - should be preferred to avoid the detrimental effect of antithyroid drugs in high- and low-dose radioiodine therapy, respectively. METHODS: We explored the effects of carbimazole on the 1-year post-radioiodine success and hypothyroidism rates by continuous dose-effect models, whereas success was defined as elimination of hyperthyroidism. Euthyroidism rates with and without carbimazole were calculated by numerical integration of the area between success and hypothyroidism curves. Target dose amplification factors for equal chance of success with and without carbimazole were calculated using logistic regression. RESULTS: Two hundred and twenty-eight patients were included in this study. Radioiodine target doses between 33 and 839 Gy were applied. Overall, the euthyroidism rates were 16.5% and 64.8%, while the hypothyroidism rates were 37.6% and 14.8% in Graves' disease and toxic nodular goitre, respectively. The success rate with simultaneous carbimazole (median dose 15 mg day(-1); range 2.5-60 mg day(-1)) was reduced over the entire target dose range in Graves' disease and toxic nodular goitre. The areas between curves for euthyroidism without and with simultaneous carbimazole were 127 and 43 Gy in Graves' disease and 178 and 128 Gy in toxic nodular goitre. The estimated radioiodine target dose amplification factor was 5.5 for Graves' disease and 3.0 for toxic nodular goitre. CONCLUSIONS: Simultaneous carbimazole reduces the euthyroidism rate, the aim of low-dose radioiodine therapy, over the entire target dose range in both Graves' disease and toxic nodular goitre. Therefore, antithyroid drug discontinuation should be preferred in low-dose radioiodine therapy. Conversely, escalation of the target dose should be preferred in high-dose radioiodine therapy.

Stunning and left ventricular function--how long is the ventricle knocked out? Left ventricular function correlated with ischemic burden and recovery time after stress.

PURPOSE: Little is known about the relation between severity of ischemia and duration of myocardial stunning. The aim of this study was therefore to characterize the impact of ischemia on myocardial stunning and on its duration. METHODS: 310 patients (pts) who underwent myocardial perfusion SPECT (MPS) were evaluated. MPS acquired with a rest Thallium/stress Technetium-99m sestamibi protocol were scored with respect to % myocardium ischemic. Left ventricular post-stress ejection fraction (psEF) was evaluated by the widely used QGS algorithm. Resting LVEF (rEF) was assessed by invasive ventriculography. Patient groups were then compared with respect to different extents of ischemia and different time intervals between stress and imaging (< or = 60 min and > 60 min after stress). RESULTS: 21% of pts had a normal MPS, 8% had evidence of scar, 37% had evidence of ischemia, and 34% had evidence of scar plus ischemia. Pts with normal MPS had a significantly higher psEF than pts with ischemia, 61+/-8% and 56+/-8%, respectively (p=0.006), whereas rEF was not different. Overall, pts with < or = 10% myocardium ischemic had significantly higher psEF than pts with > 10% myocardium ischemic, 53+/-11% and 49+/-9%, respectively (p=0.006), whereas rEF was not different. In pts with evidence of ischemia who underwent imaging < or = 60 min after stress testing, pts with < or = 10% myocardium ischemic had higher psEF than pts with > 10% myocardium ischemic, 60+/-7% and 53+/-8%, respectively (p=0.037). In contrast, pts with evidence of ischemia who underwent imaging > 60 min after stress testing had similar psEF irrespective of extent of ischemia (53%+/-8 in pts with < or = 10% ischemia and 54%+/-8 in pts with > 10% myocardium ischemic, p=0.12). CONCLUSIONS: Ischemia had a significant impact on psEF in patients who underwent imaging less than 1 h after stress. More than one hour after stress testing stunning seems to be less relevant in the interpretation of psEF.

Radioiodine uptake and thyroid hormone levels on or off simultaneous carbimazole medication: a prospective paired comparison.

AIM: To allow radioiodine (RAI) treatment in patients with need for anti-thyroid drug medication and low RAI uptakes we investigated the feasibility of discontinuing carbimazole for 3 days to enhance the RAI uptake without concurrent exacerbation of hyperthyroidism. METHODS: We prospectively investigated RAI dynamics and thyroid hormone concentration in 12 patients with low RAI uptake (<30%) under simultaneous carbimazole medication and 3 days after discontinuation. At both time points fT(4), T(3) and TSH were monitored. RESULTS: Discontinuation of carbimazole for 3 days led to a significant increase of RAI uptake in all patients. We found an enhancement up to 4.9-fold compared to the measurement on carbimazole. The mean RAI uptake increased from 15.2 +/- 4.4% to 50.1 +/- 15.5% (p<0.001). The intrapersonal radioiodine half-life increased from 4.2 +/- 1.6 days to 5.4 +/- 0.7 days (p = 0.13). Mean thyroid hormone concentration was not affected by the three day withdrawal of anti-thyroid drugs and no patient suffered from an aggravation of biochemical hyperthyroidism. CONCLUSION: A withdrawal of carbimazole for 3 days is long enough to provide sufficiently high RAI uptakes for RAI treatment in patients with low RAI uptakes and short enough to avoid the risk of exacerbation of hyperthyroidism.

Radioiodine therapy in hyperthyroidism: inverse correlation of pretherapeutic iodine uptake level and post-therapeutic outcome.

BACKGROUND: High iodine uptake levels are widely accepted as a condition for successful treatment with radioiodine (RAI). However, the existing data are controversial and the correlation of pretherapeutic RAI uptake level and outcome of RAI therapy has not yet been quantified. The aim of this study was to analyze the influence of RAI uptake on the outcome after RAI treatment and to estimate uptake-dependent success rates. MATERIALS AND METHODS: We retrospectively analyzed 229 patients (m = 53, f = 176; age 64 +/- 14 years) suffering from toxic adenoma, multinodular goitre or Graves' disease, respectively. Clinical status and T3, fT4 and TSH levels were assessed 3, 6, 12 and 18 months after treatment. Successful treatment was defined as loss of hyperthyroidism 18 months after radioiodine therapy. Logistic regression was used to assess the relation between the maximum iodine uptake and the rate of success and hypothyroidism, respectively, after RAI treatment. RESULTS: Overall, patients presented with pretherapeutic RAI uptake values between 17% and 100%. Eighteen months after RAI treatment, an euthyroid state was achieved in 136 patients (60%), hypothyroidism occurred in 47 patients (20%) and 46 patients (20%) remained hyperthyroid. The patients with the lowest pretherapeutic RAI uptakes showed the highest success rates. The overall success rate significantly decreased from 92% at low RAI uptakes to 57% at high uptakes (P = 0.002). This effect was found in the patients suffering from multinodular goitre as well as in the patients with Graves' disease. CONCLUSION: In contrast to the current opinion, our results provide evidence that the pretherapeutic iodine uptake level and post-therapeutic outcome are inversely correlated.

[Noninvasive cardiac diagnosis for quantifying scarring, ischemia and pump function within the scope of a study. 20 useful facets in routine cardiology nuclear medicine practice]. / Nicht-invasive kardiale Diagnostik zur Quantifizierung von Narbe, Ischämie und Pumpfunktion im Rahmen einer Untersuchung. 20 nützliche Facetten im Alltag der kardiologischen Nuklearmedizin.

Myocardial perfusion SPECT (MPS) commonly is interpreted qualitatively and not quantitatively. Most of the prognostic literature is based on a semi-quantitative visual analysis (SQA) of MPS. However, data about the comparison between the SQA and coronary angiography (cath) is lacking. We therefore evaluated 167 patients who underwent MPS and subsequent cath. SQA using a 20 segment model was used for MPS interpretation. Patients with a small to moderate amount of ischemia (SDS < or = 4; mean 1.2 +/- 1.5) and with extensive ischemia (SDS > 4; mean 9.6 +/- 4.7) were then compared with respect to clinical and cath variables. Patients with extensive ischemia had more advanced CAD as demonstrated by several cath variables (more often triple vessel and LAD-disease). SQA therefore is a useful tool for MPS interpretation and decision making in patients with (suspected) CAD.

Radionuclide-labeled somatostatin analogues for diagnostic and therapeutic purposes in nonmedullary thyroid cancer.

Despite the fact that several recent studies report an expression of somatostatin receptors in nonmedullary thyroid cancer (non-MTC), there is still no consensus concerning the diagnostic and therapeutic usefulness of radionuclide-labeled somatostatin analogues in non-MTC. We present the results of 50 scintigraphic studies with (111)In-Pentetreotide ((111)In-P) in 48 patients with metastasizing non-MTC (n = 9 papillary, n = 9 follicular, n = 29 Hurthle cell, n = 1 insular carcinoma). The findings were compared with histology and with other imaging modalities. (111)In-P provided unequivocally positive results in 37 of 50 (74%) of the patients (27% in the 11 patients with current thyroglobulin levels <10 ng/mL and 85% in the patients with thyroglobulin >10 ng/mL). Histopathology demonstrated that maximal uptake was observed in Hurthle cell carcinoma (95% positive examinations if thyroglobulin exceeds 10 ng/mL). We also describe for the first time dosimetric and clinical data from the courses of 90Y-DOTATOC therapy in three patients with progressive, somatostatin-receptor-positive non-MTC (up to 9.3 GBq per 4 cycles). Tumor progression could not be stopped in any of the patients treated with 90Y-DOTATOC. We conclude that (111)In-P is a promising tool for whole-body diagnosis in nonradioiodine-accumulating non-MTC, especially in Hürthle cell cancer, and if 2-[18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) is not available. Although the number of patients treated with 90Y-DOTATOC is still limited, our applied treatment protocol appears to be ineffective in metastasizing non-MTC.

Successful diffusible brachytherapy (dBT) of a progressive low-grade astrocytoma using the locally injected peptidic vector and somatostatin analogue [90Y]-DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC).

We present the therapeutic effect of diffusible brachytherapy (dBT), an innovative approach for the management of symptomatic low grade gliomas [1]. This protocol uses a radiolabelled small diffusible peptidic vector which is a somatostatin analogue to target somatostatin type 2 (sst-2) receptors. The stable radioconjugate [90Y]-DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) is repeatedly injected via catheters placed into the resection cavity or into tumour nodules. We report on the four year follow-up after initiation of dBT to treat progressive disease in a patient with a complex eleven year history of fibrillary low-grade astrocytoma. The radiopharmakon was not only locally injected into the resection cavity following debulking surgery, but also administered by slow infusion technique to target recurrent and infiltrative tumour zones in the subventricular region around the inferior and posterior horns. In conclusion, peptidic vector based dBT was found to be safe, of mild and transitory toxicity, and effective in long-term tumour control.

Chronic post-traumatic osteomyelitis of the lower extremity: comparison of magnetic resonance imaging and combined bone scintigraphy/immunoscintigraphy with radiolabelled monoclonal antigranulocyte antibodies.

OBJECTIVE: A retrospective study of the validity of combined bone scintigraphy (BS) and immunoscintigraphy (IS) using (99m)Tc-labelled murine antigranulocyte antibodies (MAB) and magnetic resonance imaging (MRI) in chronic posttraumatic osteomyelitis. DESIGN AND PATIENTS: The results of MRI and combined BS/IS of 19 lesions in 18 patients (13 men, 5 women; mean age 45 years, range 27-65 years) were independently evaluated by two radiologists and one nuclear medicine physician with regard to bone infection activity and extent. The patient group was a highly selective collection of clinical cases: the average number of operations conducted because of relapsing infection was eight (range 2-27), the average time interval between the last surgical intervention and the present study was 6.5 years (range 3 months to 39 years), and from the first operation was 14 years (range 1.5-42 years). Interobserver agreement on MRI was measured by kappa statistics. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for MRI and the nuclear medicine studies. RESULTS: For MRI/nuclear medicine, a sensitivity of 100%/77%, a specificity of 60%/50%, an accuracy of 79%/61%, a PPV of 69%/58% and a NPV of 100%/71% were calculated. Four MR examinations were false positives because of postsurgical granulation tissue. A high degree of interobserver agreement was found on MRI (kappa=0.88). A low-grade infection was missed on two scintigrams, while four were false positive because of ectopic haematopoietic bone marrow, and in one examination the anatomical distortion resulted in an inaccurate assignment of the uptake leading to false positive findings. Image analysis was frequently hindered by susceptibility artefacts due to residual abrasions of metallic implants after removal of orthopaedic devices (15/18 patients); this led to limited assessment in 17% (3/18 patients). CONCLUSION: Acute activity in a chronic osteomyelitis can be excluded with high probability if the MRI findings are negative. In the first postoperative year fibrovascular scar cannot be distinguished accurately from reactivated infection on MRI and scintigraphy may improve the accuracy of diagnosis. MRI is more sensitive in low-grade infection during the later course than combined BS/IS. Scintigraphic errors due to ectopic, peripheral, haematopoietic bone marrow can be corrected by MRI.

[Validation study of the sentinel lymph node (SLN) method in invasive breast carcinoma. Personal data and review of the literature]. / Validierungsstudie des Sentinel Lymph Node (SLN) Verfahrens beim invasiven Mammakarzinom. Eigene Daten und Review der Literatur.

BACKGROUND: Axillary lymph node dissection (ALND) is an integral part in the therapy of breast cancer. Axillary lymph node involvement and tumour size are the most important prognostic factors. Restriction of ALND to level I and II (Berg) reduced high morbidity. The increasing proportion of patients with early breast cancer and negative axillary nodes led to a more selective method to avoid unnecessary ALND. The sentinel lymph node (SLN)--the first draining lymph node of a tumour--represents the status of the axilla. A negative SLN prevents from further completion ALND. PATIENTS AND METHODS: From 9/97 to 1/99 44 patients with invasive breast cancer underwent a prospective trial of lymphatic mapping with isosulfanblue and/or lymphoscintigraphy with 99m technetium-labelled human colloid. During the operation a hand-held gamma probe was used for detection. The SLN was removed selectively and examined by routine histopathology (H&E) and immunohistochemistry (IHC). ALND of level I and II was performed in all patients for correlation. RESULTS: The SLN were identified in 41 of 44 patients (93%). 2.4 SLN per patient were harvested, overall 17.6 axillary lymph nodes. Of the 41 patients, 21 patients had positive, 20 patients negative SLN. In the 20 patients with negative SLN only one patient (5%) had metastatic disease on complete dissection (negative predictive value of 95%). In 17 patients with positive axillary lymph nodes 16 were found to have positive SLN, only one SLN was negative (false negative rate of 5.9%). In two of 41 patients micrometastases were detected by IHC. Lymphoscintigraphy revealed drainage to the axilla and internal mammary nodes in two of 28 cases (7%). SUMMARY: Our validation study proves the reproducibility and reliability of the SLN procedure. A multidisciplinary approach is indispensable. The SLN procedure has the potency for becoming the selection criterion whether to perform an ALND or not. Multiple sections and IHC staining improve the detection rate of metastatic disease. Ongoing long time investigations will determine the impact on overall survival. Our own data are discussed in an extended review of the literature.