[Lymph kinetics with technetium-99m labeled radiopharmaceuticals. Animal studies]. / Lymphkinetik mit Technetium-99m-markierten Radiopharmaka: tierexperimentelle Untersuchungen.

UNLABELLED: Aim of this study was to characterize suitable technetium-99m labeled tracers for lymphoscintigraphy by comparative animal tests. ANIMALS, METHODS: To evaluate the influence of the particle size and the organ tracer-uptake on lymphtransport animal experiments were performed on six different agents (including one control group). Activity distributions were examined in Sprague-Dawley-rats by lymphoscintigraphy; the maximum uptake (count-rate) of the whole body and in lymph nodes were analyzed by regions-of-interest-technique, respectively. Additionally, for characterization of lymphatic and extralymphatic traceruptake an intra-individual relative count-rate ratio of the liver, lung, kidneys, and spleen has been calculated following organ extraction. RESULTS: Organ specific differences of distribution were clearly demonstrated. Our results indicate that the kinetics of lymphoscintigraphic (99m)Tc-bound agents substantially depends on particle size. Reliable transport from the interstitium to initial lymph vessels and lymph node uptake suggested for tracers suited for lymphoscintigraphy a median size of about <100 nm. CONCLUSION: Our data could improve standardization of diagnostic methods and lead to an objective consideration of therapeutic procedures.

[18F]FDG imaging of head and neck tumours: comparison of hybrid PET and morphological methods.

The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose ([(18)F]FDG) imaging of head and neck tumours using a second- or third-generation hybrid PET device. Results were compared with the findings of spiral computed tomography (CT) and magnetic resonance imaging (MRI), and, as regards lymph node metastasis, the ultrasound findings. A total of 116 patients with head and neck tumours (83 males and 33 females aged 27-88 years) were examined using a hybrid PET scanner after injection of 185-350 MBq of [(18)F]FDG (Picker Prism 2000 XP-PCD, Marconi Axis gamma-PET(2) AZ). Hybrid PET examinations were performed in list mode using an axial filter. Reconstruction of data was performed iteratively. Ninety-six patients underwent CT using a multislice technique (Siemens Somatom Plus 4, Marconi MX 8000), 18 patients underwent MRI and 100 patients were examined by ultrasound. All findings were verified by histology, which was considered the gold standard, or, in the event of negative histology, by follow-up. Correct diagnosis of the primary or recurrent lesion was made in 73 of 85 patients using the hybrid PET scanner, in 50 of 76 patients on CT and in 7 of 10 patients on MRI. Hybrid PET successfully visualised metastatic disease in cervical lymph nodes in 28 of 34 patients, while 23 of 31 were correctly diagnosed with CT, 3 of 4 with MRI and 30 of 33 with ultrasound. False positive results regarding lymph node metastasis were seen in three patients with hybrid PET, in 14 patients with CT and in 13 patients with ultrasound. MRI yielded no false positive results concerning lymph node metastasis. In one patient, unrecognised metastatic lesions were seen on hybrid PET elsewhere in the body (lung: n=1; bone: n=1). Additional malignant lesions at sites other than the head and neck tumour were found in three patients (one patient with lung cancer, one patient with pelvic metastasis due to a carcinoma of the prostate and one patient with pulmonary metastasis due to breast cancer). It is concluded that [(18)F]FDG PET with hybrid PET scanners is superior to CT and MRI in the diagnosis of primary or recurrent lesions as well as in the assessment of lymph node involvement, whereas it is inferior to ultrasound in the detection of cervical lymph node metastasis.

Breast cancer: monitoring response to neoadjuvant chemotherapy using Tc-99m sestamibi scintimammography.

BACKGROUND: Aim of the study was to assess the value of scintimammography using Tc-99m sestamibi in the evaluation of tumor response to neoadjuvant chemotherapy. MATERIAL ANS METHODS: Results were calculated for 9 patients undergoing neoadjuvant chemotherapy. Scintimammography using 740 MBq Tc-99m sestamibi was performed before, during and after chemotherapy, and sestamibi uptake was scored visually and semiquantitatively to evaluate tumor response. RESULTS: In the case of complete response (n = 3) sestamibi uptake decreased 8 days after beginning neoadjuvant chemotherapy and normalized in the following course. Focal uptake decreased more slowly in patients with partial response (n = 3), who showed clear, persisting tracer accumulation after therapy. The patients without response (n = 3) showed a persisting high tumor activity even after chemotherapy was completed. CONCLUSIONS: The preliminary data suggest that in contrast to other imaging modalities scintimammography appears to yield early information regarding tumor response to neoadjuvant chemotherapy.

[Breast scintigraphy using 99mTc-sestamibi--use and limitations]. / Die Szintigraphie der Mamma mit 99mTc-Sestamibi--Indikationen und Limitationen.

AIM: Until now scintimammography did not achieve any definite role in the assessment of breast lesions. Purpose of this study was to elaborate its use as well as the limitations of scintimammography after 500 examinations completed. METHODS: Scintigraphic findings were correlated with the histopathologic outcome of 219 patients, who underwent surgery or biopsy for histopathological confirmation. The results were determined with respect to palpability of the lesion and tumour size. Additionally, a distinct analysis was performed for the patient subpopulation with indeterminate results of previously performed physical examination, mammography, and sonography. RESULTS: Overall sensitivity for scintimammography was 82.1% at a specificity of 87.5%. For palpable lesions sensitivity was 91.7% which was evidently higher as compared to 64.9% for non palpable lesions. For palpable lesions specificity was 81.1% and 88.6% for non palpable lesions. According to tumour size sensitivity ranged between 65.2% for carcinoma with a diameter < 1 cm and 93.7% for carcinoma > 1 cm. In the patients subgroup with indeterminate preliminary diagnosis (n = 143) sensitivity decreased to 71.7% at a specificity of 87.8%. Patients undergoing neoadjuvant chemotherapy showed decreasing sestamibi uptake as early as 8 days after therapy if tumour response was evident. However, small residual invasive tumours in patients with complete remission could not be visualised. CONCLUSION: Scintimammography is neither suited for screening, nor early diagnosis of breast cancer, nor for the further evaluation of small and unclear mammographic findings. Scintimammography should not be used whenever histopathological clarification of a suspicious lesion is necessary. It is useful to further investigate patients with unclear or probably benign findings in physical examination and/or mammography and to monitor tumour response to neoadjuvant chemotherapy.

[[F-18]FDG imaging of head and neck tumors: comparison of hybrid PET, dedicated PET and CT]. / [F-18]FDG-Bildgebung bei Kopf-Hals-Tumoren: vergleichende Untersuchungen mit Hybrid-PET, Ring-PET und CT.

AIM: Aim of the study was to evaluate [F-18]FDG imaging of head and neck tumors using a Hybrid-PET device of the 2nd or 3rd generation. Examinations were compared to dedicated PET and Spiral-CT. METHODS: 54 patients suffering from head and neck tumors were examined using dedicated PET and Hybrid-PET after injection of 185-350 MBq [F-18]FDG. Examinations were carried out on the dedicated PET first followed by a scan on the Hybrid-PET. Dedicated PET was acquired in 3D mode, Hybrid-PET was performed in list mode using an axial filter. Reconstruction of data was performed iteratively on both, dedicated PET and Hybrid-PET. All patients received a CT scan in multislice technique. All finding have been verified by the goldstandard histology or in case of negative histology by follow up. RESULTS: Using dedicated PET the primary or recurrent lesion was correctly diagnosed in 47/48 patients, using Hybrid-PET in 46/48 patients and using CT in 25/48 patients. Metastatic disease in cervical lymph nodes was diagnosed in 17/18 patients with dedicated PET, in 16/18 patients with Hybrid-PET and in 15/18 with CT. False positive results with regard to lymph node metastasis were seen with one patient for dedicated PET and Hybrid-PET, respectively, and with 18 patients for CT. In a total of 11 patients unknown metastatic lesions were seen with dedicated PET and with Hybrid-PET elsewhere in the body. Additional malignant disease other than the head and neck tumor was found in 4 patients. CONCLUSION: Using Hybrid-PET for [F-18]FDG imaging reveals a loss of sensitivity and specificity of about 1-5% as compared to dedicated PET in head and neck tumors. [F-18]FDG PET with both, dedicated PET and Hybrid-PET is superior to CT in the diagnosis of primary or recurrent lesions as well as in the assessment of lymph node involvement.

18F-FDG PET and 99mTc-sestamibi scintimammography for monitoring breast cancer response to neoadjuvant chemotherapy: a comparative study.

Presurgical neoadjuvant chemotherapy has shown promise in the treatment of locally advanced breast carcinoma (LABC). Response assessment by clinical examination and mammography is difficult. This study evaluated and compared fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and technetium-99m sestamibi scintimammography (SMM) as potential methods for the early assessment of tumour response to neoadjuvant chemotherapy in patients with LABC. Seven patients underwent PET and SMM [planar and single-photon emission tomography (SPET)] before beginning chemotherapy, after the first and second cycles of chemotherapy and after completing chemotherapy prior to surgery. PET and SMM results were evaluated visually and semi-quantitatively by calculating standardised uptake values (SUV) and tumour/lung ratios in the initial and subsequent studies. The findings were correlated with the initial clinical and mammographic findings and the final histopathological diagnoses. There was a highly significant correlation between SUVmean, SUVmax and the tumour/lung ratio determined with SMM-SPET in the studies performed before and during neoadjuvant chemotherapy. All three patients with complete remission showed decreasing FDG and sestamibi uptake as early as 8 days after therapy. In the presurgical study, increased sestamibi and FDG uptake was no longer evident. Three patients had partial remission with clearly reduced but persisting focal FDG and sestamibi uptake after neoadjuvant therapy. One patient who did not respond to therapy had unchanged intense tracer uptake during chemotherapy that was evident with both techniques. An early decline in glucose metabolism or sestamibi uptake 8 days after beginning therapy did not necessarily predict complete tumour remission in the further course of chemotherapy. On the other hand, increased tracer uptake after the first cycle did not exclude a partial tumour response. After the second chemotherapeutic cycle both techniques were able to distinguish between complete and partial/no response. There was a good correlation between preoperative FDG and sestamibi uptake and the histopathologically determined tumour size. However, small residual invasive tumours in patients with clinically complete remission could not be visualised with either technique. The preliminary data demonstrate that sestamibi SMM is as useful as FDG-PET for the monitoring of tumour response to neoadjuvant chemotherapy.

Is a low-dose Tc-99m-MIBI protocol suitable for first-pass RNV?

Tc-99m-labelled radiopharmaceuticals, such as Tc-99m-sestamibi (Tc-99m-MIBI), offer the opportunity to measure myocardial perfusion and function with one injection only. The aim of this study was to evaluate whether first-pass (FP) radionuclide ventriculography (RNV) consecutively followed by myocardial perfusion single photon emission computed tomography (SPECT) may be performed according to a low-dose MIBI 1-day protocol using a multi-crystal gamma camera. Two hundred and seventy consecutive, predominantly obese [61% with a body mass index (BMI) of >25 kg x m(-2)] patients (169 male, 101 female), referred for myocardial perfusion SPECT with Tc-99m-MIBI [4 MBq x kg(-1) (>300 MBq) at stress; 9 MBq x kg(-1) (> 650 MBq) at rest], were studied with FP RNV prior to SPECT. Bicycle ergometry (29%), dobutamine (6%) or dipyridamole stress (65%) was performed. Adequate count (ct) statistics for FP RNV were defined as follows: (1) > 2000 cts within the background-corrected, end-diastolic (ED), left ventricular (LV) region of interest (ROI) of the representative cycle; and (2) >4 heart beats with > 1000 cts within the ED LV ROI (> 50% of maximal cts). A net mean dose of 318+/-64 MBq (4.3+/-1.1 MBq x kg(-1)) was injected during stress and 674+/-55 MBq (9.1+/-1.7 MBq x kg(-1)) during rest. There was no statistical difference among the three stress modalities concerning the net dose. Two hundred and fifty-six out of 270 (95%) stress and a basis for reliable all 270 (100%) rest FP RNV studies showed adequate count statistics as functional analysis. The 14 patients with insufficient count statistics were all obese and had received less than the planned dose. For the vast majority of patients, even a low-dose 1-day protocol with Tc-99m-MIBI is suitable for the assessment of FP RNV prior to SPECT. A minimum of 300 MBq and 4 MBq x (kg body weight)(-1) should be administered in order to obtain technically adequate results even in obese patients.

Attention deficit hyperactivity disorder: binding of [99mTc]TRODAT-1 to the dopamine transporter before and after methylphenidate treatment.

Involvement of the dopaminergic system has been suggested in patients suffering from attention deficit hyperactivity disorder (ADHD) since the symptoms can be successfully treated with methylphenidate, a potent blocker of the dopamine transporter (DAT). This study reports the findings on the status of the DAT in adults with ADHD before and after commencement of treatment with methylphenidate, as measured using [99mTc]TRODAT-1. Seventeen patients (seven males, ten females, aged 21-64 years, mean 38 years) were examined before and after the initiation of methylphenidate treatment (3x5 mg/day). All subjects were injected with 800 MBq [99mTc]TRODAT-1 and imaged 3 h p.i. Single-photon emission tomography (SPET) scans were acquired using a triple-headed gamma camera. For semiquantitative evaluation of the DAT, transverse slices corrected for attenuation were used to calculate specific binding in the striatum, with the cerebellum used as background [(STR-BKG)/BKG]. Data were compared with an age-matched control group. It was found that untreated patients presented with a significantly increased specific binding of [99mTc]TRODAT-1 to the DAT as compared with normal controls [(STR-BKG)/BKG: 1.43+/-0.18 vs 1.22+/-0.06, P<0.001]. Under treatment with methylphenidate, specific binding decreased significantly in all patients [(STR-BKG)/BKG: 1.00+/-0.14, P<0.001]. Our findings suggest that the number of DAT binding sites is higher in drug-naive patients suffering from ADHD than in normal controls. The decrease in available DAT binding sites under treatment with methylphenidate correlates well with the improvement in clinical symptoms. The data of this study help to elucidate the complex dysregulation of the dopaminergic neurotransmitter system in patients suffering from ADHD and the effect of treatment with psychoactive drugs.