Tomohiro Takiguchi

Bone metabolic markers in bone metastases

The efficacy and cost/performance benefit of radionuclide bone scintigraphy in monitoring metastatic bone activity remain controversial. Recently developed bone metabolic markers are expected to play an additional role in the diagnosis of bone metastasis. We measured osteoclastic and osteoblastic markers in 267 patients with breast cancer (100 with bone metastasis), 38 patients with prostatic cancer (25 with bone metastasis), 50 patients with lung cancer (12 with bone metastasis) and 33 patients with miscellaneous cancers (13 with bone metastasis) and compared the values in the presence and absence of bone metastasis. Bone metabolic markers, both osteoclastic and osteoblastic, increased significantly in patients with bone metastasis. In breast cancer (bone metastasis is mostly of the mixed type), osteoclastic markers were good in detecting bone metastasis. In prostatic cancer (bone metastasis is mostly osteoblastic), osteoclastic and osteoblastic markers were equally effective in detecting bone metastasis. In lung cancer (bone metastasis is mostly osteolytic), osteoclastic markers were elevated preferentially in bone metastasis. Over all, osteoclastic markers were more sensitive in the diagnosis of bone metastasis, and among osteoclastic markers, serum pyridionoline-cross-linked carboxyterminal telopeptide was the most efficient in both specificity (91.0%) and sensitivity (48.6%) for detecting bone metastasis.

Radioguided sentinel node detection in breast cancer patients: comparison of 99mTc phytate and 99mTc rhenium colloid efficacy.

BackgroundRadioguided sentinel node biopsy (SNB) of breast cancer patients has become a standard method for detecting early stage breast cancer. However, no standard radiopharmaceutical exists. Methods99mTc rhenium colloid or 99mTc phytate SNB was used to aid detection in breast cancer patients. For each radiopharmaceutical, 100 patients were examined. The following points were compared: (1) scintigraphic detection rate of axillary sentinel nodes (detectability and number when detectable) and internal mammary sentinel nodes; (2) the number of nodes detected scintigraphically and the number detected during surgery; (3) sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for axillary sentinel nodes. ResultsAxillary sentinel nodes of patients were biopsied using either 99mTc rhenium or 99mTc phytate. The number of axillary nodes surgically removed from patients given 99mTc rhenium was 2.28±1.08 (mean±SD), and the number of axillary nodes surgically removed from patients given 99mTc phytate was 1.68±0.82. Some patients given 99mTc rhenium showed a spill-over of radioactivity from sentinel nodes. Concordance of scintigraphically detected nodes and surgical removed nodes was superior for 99mTc phytate compared to that with 99mTc rhenium, with a statistically significant difference. The sensitivity and negative predictive value was superior with 99mTc phytate compared to that with 99mTc rhenium, even though no statistical difference was detectable. However, visualization of internal mammary nodes was superior with 99mTc rhenium. ConclusionIn breast cancer patients, 99mTc phytate is a better choice for the detection of axillary SNB than 99mTc rhenium colloid. However, 99mTc rhenium colloid is a better choice for the detection of internal mammary nodes.

An easy and reproducible semi-automatic method for the evaluation of99mTc-galactosyl human serum albumin

Abstract99mTc-galactosyl human serum albumin (99mTc-GSA) scintigraphy is a new method for evaluating liver function. This scintigraphy is useful for evaluating the severity of liver diseases. The indices evaluating hepatic function include the receptor index (LHL15) and the index of blood clearance (HH15). These indices are calculated on the basis of the regions of interest (ROIs) for both whole liver and heart, and are susceptible to the ROIs over heart and liver. At present, there is no standard method for determining ROIs. We attempted to establish a standard method which shall not be subject to inter and/or intra operator variation. A computer program to determine heart and liver ROIs semi-automatically was developed. Ten patients (12 instances) were studied with99mTc-GSA, and HH15 and LHL15 were calculated on the basis of the ROIs obtained manually and semiautomatically by 3 different operators independently. Blood sampling and gamma-counting yielded blood clearance data. The ICG R15 was compared with each index in 34 patients. The time needed for ROI determination was reduced from 2–3 minutes for the manual method to 0.5–0.8 minutes for the semi-automatic method. The % coefficients of variation (% CVs) of HH15 and LHL15 were improved in the order manual-inter observer (M-inter), manual-intra observer (M-intra) and semiautomated-inter observer (SA-inter); % CVs of HH15 were 2.26% for M-inter, 1.55% for M-intra and 0.07% for SA-inter, and % CVs of LHL15 were 2.29% for M-inter, 0.46% for M-intra and 0.07% for SA-inter. The correlation of HH15 and LHL15 among M-inter, M-intra and SA-inter was good. Comparison of indices obtained by manual and semi-automatic methods with blood clearance data obtained by blood sampling and gamma-counting showed good correlations and no significant differences. The comparison with ICG R15 showed that HH15 and LHL15 by the semi-automated method gave better correlation that that by the manual method. A newly developed semi-automated method improved data processing time and deviation of indices in99mTc-GSA studies. This method should substitute for manual ROI determination.

Evaluation of bone metastatic burden by bone SPECT/CT in metastatic prostate cancer patients: defining threshold value for total bone uptake and assessment in radium-223 treated patients

ObjectivesTo establish a new three-dimensional quantitative evaluation method for bone metastasis, we applied bone single photon emission tomography with computed tomography (SPECT/CT). The total bone uptake (TBU), which measures active bone metastatic burden, was calculated as the sum of [mean uptake obtained as standardized uptake value (SUV) above a cut-off level] × (the volume of the lesion) in the trunk using bone SPECT/CT. We studied the threshold value and utility of TBU in prostate cancer patients treated with radium-223 (Ra-223) therapy.MethodsTo establish the threshold value of TBU, we compared bone metastatic and non-metastatic regions in 61 prostate cancer patients with bone metastasis and 69 without. Five fixed sites in each patient were selected as evaluation points and divided into bone metastatic and non-metastatic sites. Sensitivity and specificity analysis was applied to establish the threshold level. Using the obtained threshold value, we then calculated the TBU in nine prostate cancer patients who received Ra-223 therapy, and compared the results with the bone scan index (BSI) by BONENAVI® and visual evaluation of bone scintigraphy.ResultsUptake was significantly lower in non-metastatic sites in patients with bone metastasis than in patients without metastasis. Sensitivity and specificity analysis revealed SUV = 7.0 as the threshold level. There was a discrepancy between TBU and BSI change in two of the nine patients, in whom TBU change correlated with visual judgement, but BSI change did not. In two patients, BSI was nearly 0 throughout the course, but the TBU was positive and changed, although the change was not large. These results suggest that TBU may be more accurate and sensitive than BSI for quantitative evaluation of active bone metastatic burden.ConclusionWe established a threshold value (SUV > 7.0) for three-dimensional TBU for evaluating active bone metastatic burden in prostate cancer patients using bone SPECT/CT. Despite the small number of patients, we expect the change in TBU could be more accurate and sensitive than the change in BSI among patients who received Ra-223.

Validation of Cross-calibration Schemes for Quantitative Bone SPECT/CT Using Different Sources under Various Geometric Conditions

PURPOSE Several cross-calibration schemes have been proposed to produce quantitative values in bone SPECT imaging. Differences in the radionuclide sources and geometric conditions can decrease the accuracy of cross-calibration factor (CCF). The present study aimed to validate the effects of calibration schemes using different sources under various geometric conditions. METHODS Temporal variations as well as variations in acquisition counts and the shapes of 57Co standard and 99mTc point sources and a 99mTc disk source were determined. The effects of the geometric conditions of the source-to-camera distance (SCD) and lateral distance on the CCF were investigated by moving the camera or source away from the origin. The system planar sensitivity of NEMA incorporated into a Symbia Intevo SPECT/CT device (Siemens®) was defined as reference values. RESULTS The temporal variation in CCF using the 57Co source was relatively stable within the range of 0.7% to 2.3%, whereas the 99mTc source ranged from 2.7% to 7.3%. In terms of source shape, the 57Co standard point source was the most stable. Both SCD and lateral distance decreased as a function of distance from the origin. Errors in the geometric condition were higher for the 57Co standard point source than the 99mTc disk source. CONCLUSIONS Different calibration schemes influenced the reliability of quantitative values. The 57Co standard point source was stable over a long period, and this helped to maintain the quality of quantitative SPECT/CT imaging data. The CCF accuracy of the 99mTc source decreased depending on the preparative method. The method of calibration for quantitative SPECT should be immediately standardized to eliminate uncertainty.

A Comparison of Planar Sensitivity and Spatial Resolution among Different Collimators and Energy Windows on 223 Ra Imaging

OBJECTIVE The present study aimed to reveal the influence of combination of different collimators and energy windows on the planar sensitivity and the spatial resolution during experimental 223Ra imaging, and to determine optimal imaging parameters. METHODS A vial type source containing 223Ra solution (4.55 MBq / 5.6 ml) was placed in the air at 100 mm away from the collimator surface. Planar images were acquired with LEHR, LMEGP, ELEGP and MEGP collimators on two dual-head gamma cameras (Symbia intevo (Siemens) and Infinia 3 (GE)). We compared three energy window combinations: 1) single window at 82 keV, 2) double window at 82+154 keV, 3) triple window at 82+154+270 keV. The energy spectrum, the sensitivity and the spatial resolution, such as full-width at half-maximum (FWHM) and full-width at tenth-maximum (FWTM), of each collimator were assessed. RESULTS Five energy spectra (at around 82, 154, 270, 351 and 405 keV) were essentially observed among four collimators. The sensitivity was high for LEHR collimator, then ELEGP and LMEGP collimator was 3-4 fold, which is greater than MEGP collimator. The 82 keV energy window of four collimators has best spatial resolution. Moreover, the spatial resolution of the 82 keV energy window with LMEGP and ELEGP collimator was almost equal to that of the triple window with MEGP collimator. CONCLUSIONS Optimal imaging parameters were single energy window using LMEGP or ELEGP, and then triple energy window using MEGP collimator.