OBJECTIVE:

The aim of this study was to measure the apparent diffusion coefficient (ADC) value at the region with the highest FDG uptake using sequential (18)F-FDG PET and MRI, and to correlate it with the histological grade of invasive ductal carcinoma (IDC) of the breast.

METHODS:

A retrospective study was conducted on 75 untreated patients with IDC. First, a PET/CT scan and subsequent breast MRI were done and the SUVmax of the each breast tumor was recorded. Then, a PET image and ADC map were co-registered. On the axial slice containing the pixel with SUVmax, we drew multiple circular ROIs within the tumor and measured the mean ADC value of each ROI. The average (ADC-mean) and minimum (ADC-min) of the mean ADC values for all ROIs within the tumor were calculated, respectively. Then, a circular ROI was placed at the corresponding location to the pixel with the highest SUV and the mean ADC value of the ROI was denoted as ADC-PET. We compared the averages of the ADC parameters and assessed the correlations among SUVmax and ADC parameters. ROC curve and logistic regression analyses were performed to assess the utility of ADC and SUVmax for detecting histological grade 3.

RESULTS:

ADC-min was significantly lower than the ADC-mean or ADC-PET. All of the ADC parameters showed a negative correlation with SUVmax. The area under the ROC curve for identifying histological grade 3 using ADC-PET, ADC-min, ADC-mean and SUVmax was 0.684, 0.660, 0.633 and 0.639, respectively. By multivariate analysis, ADC-PET was a significant, independent predictor of histological grade 3 (p = 0.004).

CONCLUSIONS:

We estimated the ADC value at the breast tumor region with the highest FDG uptake using sequential (18)F-FDG PET and MRI. This new ADC parameter distinguished high-grade IDC, supporting the feasibility of the combined PET-MRI system in patients with breast cancer.

OBJECTIVES:

The aim of the study is to improve the spatial resolution of SPECT images acquired with a fan-beam collimator.

METHODS:

The aperture angle of a hole in the fan-beam collimator depends on the position of the collimator. To correct the aperture effect in an iterative image reconstruction, an asymmetrically trimmed Gaussian weight was used for a model. To confirm the validity of our method, point source phantoms and brain phantom were used in the simulation, and we applied the method to the clinical data.

RESULTS:

The results of the simulation showed that the spatial resolution of point sources improved from about 6 to 2 pixels full width at half maximum, and the corrected point sources were isotropic. The results of the simulation with the brain phantom showed that our proposed method could improve the spatial resolution of the phantom, and our method was effective for different fan-beam collimators with different focal lengths. The results of clinical data showed that the quality of the reconstructed image was improved with our proposed method.

CONCLUSIONS:

Our proposed aperture correction method with the asymmetrically trimmed Gaussian weighting function was effective in improving the spatial resolution of SPECT images acquired with the fan-beam collimator.

OBJECTIVE:

Our final goal is to develop an appropriate method using nuclear medicine technique for monitoring the effect and prediction of Photodynamic Therapy (PDT) on tumors. The aim of this study is to evaluate the effect of PDT on tumor cells in vitro using (18)F-FDG and (99m)Tc-MIBI as tracers.

METHODS:

Five tumor cell lines (A431, DU145, H1650, LS180, SHIN3) with varied characteristics were irradiated after incubating for 24 h with several doses of Photofrin (PF). Singlet oxygen was monitored by the near-IR emission detection system during irradiation and generated (1)O2 was calculated. PDT effects were rapidly evaluated by nuclear medicine techniques (uptake of (18)F-FDG and (99m)Tc-MIBI) and traditional methods for cell viability (MTT and trypan blue assays) at 3 h after PDT. Intracellular PF concentration was measured by absorption spectrometer and cell protein content was measured by the Lowry method. (18)F-FDG uptake, (99m)Tc-MIBI uptake, singlet oxygen, and intracellular PF concentration were standardized by protein content. Decrease % of (18)F-FDG and (99m)Tc-MIBI, MTT, and trypan blue was normalized to the control group.

RESULTS:

Decrease % of (18)F-FDG was exponentially related to decrease % of MTT (R (2) = 0.650, P < 0.01) while decrease % of (99m)Tc-MIBI was linearly related to that of MTT (R (2) = 0.719, P < 0.01). The decrease % of MTT was more sensitive than that of trypan blue. However, neither (1)O2 nor PF uptake was correlated with sensitivity to PDT. In addition, (18)F-FDG uptake before PDT was linearly related to decrease % of MTT (R (2) = 0.800, P < 0.05).

CONCLUSIONS:

Our findings in in vitro studies suggest that (99m)Tc-MIBI is better than (18)F-FDG for early evaluation of PDT effect, but (18)F-FDG uptake may be used to predict PDT sensitivity before therapy.

OBJECTIVE:

Several different somatostatin analogs labeled with gamma or positron-emitting radionuclides exist for diagnostic imaging of neuroendocrine tumors (NETs). Differences between standard diagnostic scintigraphy (SDS) and post-therapy whole-body scan (PTWBS) at peptide receptor radionuclide therapy in lesion detection are known; such differences have been correlated with the varying degree of receptor subtype expression and the varying receptor affinity profile of the different ligands. The aim of this study is to investigate differences between SDS and PTWBS obtained using the same radiopharmaceutical.

METHODS:

We retrospectively reviewed clinical records of 53 patients with a diagnosis of NET, who underwent both SDS and PTWBS using (111)In-Pentetreotide. We compared the number of lesions for each body region detected by SDS and PTWBS.

RESULTS:

In 14/53 patients (26.4 %) discrepancies between SDS and PTWBS were found. PTWBS detected 68 additional lesions with respect to SDS that were distributed as follows: head and neck, 6; mediastinum, 1; liver, 10; abdomen/pelvis, 1; bone, 44; other localizations, 6. The number of lesions detected by SDS was significantly different from that revealed by PTWBS (Wilcoxon matched pairs test, P = 0.0313). The regions that contributed significantly to reach this difference were head and neck (McNemar test, P = 0.0412), liver (McNemar test, P = 0.0044), bone (McNemar test, P < 0.0001) and other localizations (McNemar test, P = 0.0412).

CONCLUSION:

PTWBS shows more lesions than SDS with a significant discrepancy. We suppose that administration of higher radiopharmaceutical activity, use of larger peptide amount and the different time interval between radiopharmaceutical administration and scan execution can determine a higher sensitivity of PTWBS.

Whole-body positron emission tomography/computed tomography (PET/CT) with [(11)C]- and [(18)F]-labeled choline derivates has emerged as a promising molecular imaging modality for the evaluation of prostate cancer. (11)C- and (18)F-choline PET/CT are used successfully for restaging prostate cancer in patients with biochemical recurrence of disease after definitive therapy, especially when the serum prostate-specific antigen level is >1.0 ng/mL. (11)C- and (18)F-choline PET/CT have more limited roles for the initial staging of prostate cancer and for the detection of tiny lymph node metastases due to the low spatial resolution inherent to PET. Overall, these modalities are most useful in patients with a high pre-test suspicion of metastatic disease. The following is a review of the current clinical roles of (11)C- and (18)F-choline PET/CT in the management of prostate cancer.

PURPOSE:

To investigate the best standardized uptake value (SUV) index for differentiation of adrenal metastases from adrenocortical adenomas using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT).

MATERIALS AND METHODS:

A total of 129 patients (82 males and 47 females; mean age 65.4 years) with extra-adrenal primary malignancies who had known or suspected adrenal lesions underwent FDG PET/CT examinations for detection, staging, re-staging, or recurrence of tumor. Among these patients, 45 adrenal lesions (22 adenomas and 23 metastases) in 41 patients were evaluated. The maximum SUVs for adrenal lesions (adrenal SUVmax) and mean liver and spleen SUVs were recorded, and the ratio of the adrenal SUVmax to the mean liver SUV (adrenal-to-liver SUV ratio) and that of the adrenal SUVmax to the mean spleen SUV (adrenal-to-spleen SUV ratio) were obtained. Diagnostic performances for the adrenal SUVmax, adrenal-to-liver SUV ratio, and adrenal-to-spleen SUV ratio were compared.

RESULTS:

The mean adrenal SUVmax, adrenal-to-liver SUV ratio, and adrenal-to-spleen SUV ratio were higher for adrenal metastases (8.4 ± 3.8, 3.0 ± 1.3, and 4.0 ± 1.9, respectively) than for adrenocortical adenomas (2.9 ± 1.0, 0.9 ± 0.3, and 1.3 ± 0.3, respectively) (P < 0.001). The area under the curve was higher for the adrenal-to-liver SUV ratio (0.99) than for the adrenal SUVmax (0.96) and adrenal-to-spleen SUV ratio (0.98). In the differentiation of adrenocortical adenomas and adrenal metastases, an adrenal-to-liver SUV ratio cutoff value of 1.37 yielded a sensitivity of 96 % and specificity of 100 %.

CONCLUSION:

In FDG PET/CT analysis, the adrenal-to-liver SUV ratio had a greater ability to differentiate adrenocortical adenomas and adrenal metastases than did the adrenal SUVmax or adrenal-to-spleen SUV ratio.

OBJECTIVE:

Lung cancer is one of the leading causes of cancer-related deaths worldwide, including Japan. Although computed tomography (CT) can detect small lung lesions such as those appearing as ground glass opacity, it cannot differentiate between malignant and non-malignant lesions. Previously, we have shown that single photon emission computed tomography (SPECT) imaging using (111)In-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-cyclo-(Arg-Gly-Asp-D-Phe-Lys) (DOTA-c(RGDfK)), an imaging probe of αvβ3 integrin, is useful for the early detection of pancreatic cancer in a hamster pancreatic carcinogenesis model. In this study, we aimed to assess the usefulness of SPECT/CT with (111)In-DOTA-c(RGDfK) for the evaluation of the malignancy of lung cancer.

METHODS:

Lung tumors were induced by a single intraperitoneal injection (250 mg/kg) of urethane in male A/J mice. Twenty-six weeks after the urethane treatment, SPECT was performed an hour after injection of (111)In-DOTA-c(RGDfK). Following this, the radioactivity ratios of tumor to normal lung tissue were measured by autoradiography (ARG) in the excised lung samples. We also examined the expression of αvβ3 integrin in mouse and human lung samples.

RESULTS:

Urethane treatment induced 5 hyperplasias, 41 adenomas and 12 adenocarcinomas in the lungs of 8 A/J mice. SPECT with (111)In-DOTA-c(RGDfK) could clearly visualize lung nodules, though we failed to detect small lung nodules like adenoma and hyperplasias (adenocarcinoma: 66.7 %, adenoma: 33.6 %, hyperplasia: 0.0 %). ARG analysis revealed significant uptake of (111)In-DOTA-c(RGDfK) in all the lesions. Moreover, tumor to normal lung tissue ratios increased along with the progression of carcinogenesis. Histopathological examination using human lung tissue samples revealed clear up-regulation of αvβ3 integrin in well-differentiated adenocarcinoma (Noguchi type B and C) rather than atypical adenomatous hyperplasia.

CONCLUSION:

Although there are some limitations in evaluating the malignancy of small lung tumors using (111)In-DOTA-c(RGDfK), SPECT with (111)In-DOTA-c(RGDfK) might be a useful non-invasive imaging approach for evaluating the characteristics of lung tumors in mice, thus showing potential for use in humans.

OBJECTIVE:

Targeted photodynamic therapy (PDT) is necessary for preventing the side effects associated with PDT, such as photosensitivity caused by the distribution of photosensitizers into normal tissues. In the development of targeted PDT agents, a simple evaluation system of in vivo pharmacokinetics, as well as target cell uptake, is absolutely imperative. We hypothesized that (64)Cu chelation with porphyrin photosensitizer-biomacromolecule conjugates may become a simple and versatile labeling strategy for this purpose.

METHODS:

Protoporphyrin IX (PPIX) and a bombesin (BBN) analog, that interacts with the gastrin-released peptide (GRP) receptor, were used as a photosensitizer and tumor-targeting peptide, respectively. Then, a conjugate of PPIX and BBN analog linked via short polyethylene glycol (PPIX-PEG6-BBN analog) was synthesized and used as a targeted PDT agent. In addition, a (64)Cu-chelated PPIX-PEG6-BBN analog was synthesized under optimized reaction conditions. Lastly, cell uptake study and PET image-based pharmacokinetic analyses of the PPIX-PEG6-BBN analog were carried out in a human prostate cancer cell line, PC-3, which highly expresses the GRP receptor, and PC-3 tumor-bearing mice.

RESULTS:

It was confirmed that degradation (thought to be based on radiolysis) occurs, and large amounts of (64)Cu-labeling compounds are wasted in the reaction mixture. Interestingly, the addition of ethanol into the reaction mixture provides an effective solution for this problem. As for cell uptake study, the [(64)Cu]PPIX-PEG6-BBN analog demonstrated significantly higher uptake for PC-3 cells than [(64)Cu]PPIX and, in addition, the uptake of [(64)Cu]PPIX-PEG6-BBN analog was significantly inhibited by adding excess cold BBN analog peptide. PET image-based pharmacokinetic evaluation revealed that [(64)Cu]PPIX-PEG6-BBN analog and [(64)Cu]PPIX rapidly accumulate into the liver and kidney, circulate in blood for a long time compared with normal peptides, and distribute at a low level in the tumor. This result suggested that in vivo biodistribution of PPIX-PEG6-BBN analog is mainly dependent on the lipophilicity of PPIX. Ex vivo measurements of radioactivity distribution after PET studies showed that although there was no remarkable difference in the tumor/skin ratio of radioactivity between [(64)Cu]PPIX-PEG6-BBN analog and [(64)Cu]PPIX, the pancreas (an organ that also expresses GRP receptors)/skin ratio was significantly higher in the case of [(64)Cu]PPIX-PEG6-BBN analog.

CONCLUSION:

We report on the successful synthesis of (64)Cu-chelated porphyrin photosensitizers and their tumor-targeting peptide conjugates under conditions in which radiolysis is suppressed. This labeling strategy with porphyrin photosensitizers may be of value for the rapid development of ideal targeted PDT agents.

A 54-year-old woman with metastatic colorectal carcinoma underwent liver radioembolization with (90)Y resin microspheres. Microsphere biodistribution was assessed 2 h after the treatment through a 20-min long (90)Y PET scan. Isodose map and lesion dose-volume histogram (DVH) were then evaluated using a MATLAB-based code. Response to therapy was assessed performing a (18)F-FDG PET 6 months after the treatment. At (90)Y PET the patient showed a well-defined horseshoe-shaped hepatic lesion with hot margins and a cold core. The lesion presented a heterogeneous DVH with a hot margin receiving an average radiation dose as high as 287 Gy and a cold area receiving an average radiation dose of 70 Gy approximately. Six months after the treatment the patient reported a complete remission of tumour areas which received a high radiation dose, while progression of metastases was observed in the area that presented scarce microsphere localization at (90)Y PET. According to our experience, the use of (90)Y PET voxel dosimetry may provide a useful tool to assess possible correlations between microsphere biodistribution and clinical outcome of the treatment. In agreement with current literature findings, an average radiation dose greater than approximately 100 Gy may be required to sterilize liver metastases.

OBJECTIVE:

We evaluated intra- and interoperator reproducibilities in calculating the conventional indices HH15 and LHL15 from (99m)Tc-diethylenetriamine pentaacetic acid galactosyl human serum albumin ((99m)Tc-GSA) scintigraphy, and proposed new, simple methods for the calculation of quantitative indices.

METHODS:

The results of (99m)Tc-GSA scintigraphy in 33 patients were retrospectively analyzed. Heart and liver ROIs were drawn manually to cover cardiac blood pool and entire liver, respectively, and HH15 and LHL15 were calculated. In addition, square regions of interest (ROIs) of fixed sizes were placed at the highest activity in blood pool and the liver. Using the square heart ROI, sHH15, an equivalent of HH15, was computed. Fractional liver uptake at 15 min (FLU15) was calculated using the square heart and liver ROIs. Intra- and interoperator reproducibilities, as well as correlation with Indocyanine green retention rate at 15 min (ICG R15), were assessed for these four indices by linear regression analysis.

RESULTS:

Substantial intra- and interoperator variabilities were found for HH15 and LHL15. The correlation coefficients for intra- and interoperator comparisons were 0.884 and 0.869 for HH15, respectively, and 0.919 and 0.917 for LHL15, respectively. The use of square ROIs instead of hand-drawn ROIs improved reproducibility. The correlation coefficients for intra- and interoperator comparisons were 0.988 and 0.973 for sHH15, respectively, and 0.989 and 0.975 for FLU15, respectively. Correlation with ICG R15 was better for sHH15 (r = 0.619) and FLU15 (r = -0.656) than for HH15 (r = 0.439) and LHL15 (r = -0.490).

CONCLUSIONS:

HH15 and LHL15 showed substantial intra- and interoperator variabilities, and the use of square ROIs are indicated to provide better reproducibility.