Experience of rescue therapy with [177Lu]Lu-rhPSMA-10.1 in patients with primary or acquired resistance to [177Lu]Lu-PSMA-I&T.

PURPOSE: Radioligand therapy is an increasingly important option for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Radiohybrid ligands targeting prostate-specific membrane antigen (PSMA) are a novel group of theranostic radioligand therapy agents for which higher tumour absorbed radiation doses have been demonstrated compared to established PSMA ligands. Here, we report data from ten patients who were treated within a compassionate use program with the radiohybrid PSMA-ligand [177Lu]Lu-rhPSMA-10.1 after experiencing disease progression under treatment with [177Lu]Lu-PSMA-I&T. METHODS: Ten patients with advanced PSMA-positive prostate cancer who showed progression under treatment with [177Lu]Lu-PSMA-I&T received up to three cycles of rescue therapy with [177Lu]Lu-rhPSMA-10.1 (7.4-8.1 GBq per cycle). Efficacy (PSA response according to PCWG3 and RECIP) and overall survival were evaluated. Adverse events were recorded from first application. RESULTS: Despite progression with [177Lu]Lu-PSMA-I&T, after the first cycle of [177Lu]Lu-rhPSMA-10.1 rescue therapy, five patients (50%) showed a decrease in serum PSA level. In imaging, three of the ten patients (30%) showed a partial radiologic response. Four of the five patients with a decrease of serum PSA under [177Lu]Lu-rhPSMA-10.1 had initially responded to treatment with [177Lu]Lu-PSMA-I&T but had become resistant. However, the remaining patient had shown continuous disease progression during [177Lu]Lu-PSMA-I&T therapy but showed an immediate response to [177Lu]Lu-rhPSMA-10.1. The additional treatment with [177Lu]Lu-rhPSMA-10.1 was generally well tolerated by all patients. CONCLUSIONS: Patients showing tumour progression while receiving [177Lu]Lu-PSMA-I&T radioligand therapy may benefit from rescue therapy with the novel radiohybrid PSMA ligand, [177Lu]Lu-rhPSMA-10.1. Higher tumour absorbed radiation doses with [177Lu]Lu-rhPSMA-10.1 may overcome primary and acquired radiation resistance.

68Ga-PSMA I&T PET/CT for primary staging of prostate cancer.

PURPOSE: The present study is based on a retrospective analysis of Gallium-68 (68Ga)-labelled prostate-specific membrane antigen (68Ga-PSMA I&T) PET/CT performed in newly diagnosed, treatment-naïve prostate cancer (PCa) patients prior to definitive treatment. METHODS: A total of 82 men were included in the study and were imaged with 68Ga-PSMA I&T PET/CT to assess the distribution of PSMA-avid disease for staging purposes (11 with low-risk, 32 with intermediate-risk, and 39 with high-risk PCa). Forty patients (20 with intermediate- and 20 with high-risk disease) underwent subsequent radical prostatectomy with extended pelvic lymph node dissection which allowed for correlation of imaging findings with histopathologic data. RESULTS: PSMA-positive disease was detected in 83% of patients with 66/82 (80.5%) primary tumours being visualized. PSMA-avid lymph nodes were recorded in 17/82 patients (20.7%, 3 with intermediate-risk and 14 with high-risk PCa); distant disease was found in 14/82 subjects (17.1%, 2 with intermediate-risk and 12 with high-risk PCa). No extraprostatic disease was found in low-risk PCa. SUVmax of primary tumours showed a weak but significant correlation with serum PSA values (r = 0.51, p < 0.001) and Gleason scores (GSC; r = 0.35, p = 0.001), respectively. In correlation with histopathology, calculated per-region sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for detection of lymph node metastases were 35.0%, 98.4%, 63.6%, 95.0%, and 93.0%, respectively. CONCLUSIONS: In patients with initial diagnosis of intermediate- and high-risk prostate cancer, 68Ga-PSMA I&T PET/CT emerges as a relevant staging procedure by identifying nodal and/or distant metastases. Due to the low prevalence of extraprostatic disease, its value seems to be limited in low-risk disease.

Chemokine Receptor 4 Expression in Primary Sjögren's Syndrome.

Ga-pentixafor is a novel radioligand of C-X-C motif chemokine receptor 4. A 55-year-old woman with a history of primary Sjögren's syndrome underwent Ga-pentixafor PET/CT for staging of lymphoma originating from mucosa-associated lymphoid tissue. Whereas no lymphoma manifestation could be detected, imaging revealed bilateral intense radiotracer uptake in both parotid and submandibular salivary glands, consistent with inflammatory cell infiltration.

Diagnostic Performance of 11C-choline PET/CT and FDG PET/CT in Prostate Cancer.

We compared 11C-choline and FDG PET/CT scan findings for the staging and restaging of prostate cancer. Twenty Japanese prostate cancer patients underwent 11C-choline and FDG PET/CT before (n=5) or after (n=15) treatment. Using a five-point scale, we compared these scanning modalities regarding patient- and lesion-based diagnostic performance for local recurrence, untreated primary tumor, and lymph node and bony metastases. Of the 20 patients, documented local lesions, and node and bony metastases were present in 11 (55.0%), 9 (45.0%), and 13 (65.0%), respectively. The patient-based sensitivity/specificity/accuracy/area under the receiver-operating-characteristic curve (AUC) values for 11C-choline-PET/CT for diagnosing local lesions were 90.9% /100%/ 95.0% / 1.0, whereas those for FDG-PET/CT were 45.5% /100%/ 75.0% / 0.773. Those for 11C-choline-PET/CT for node metastasis were 88.9% /100%/ 95.0% / 0.944, and those for FDG-PET/CT were 44.4%/100%/75.0%/0.722. Those for 11C-choline-PET/CT for bone metastasis were 84.6%/100%/90.0%/0.951, and those for FDG-PET/CT were 76.9% /100%/ 85.0% / 0.962. The AUCs for local lesion and node metastasis differed significantly (p=0.0039, p=0.011, respectively). The lesion-based detection rates of 11C-choline compared to FDG PET/CT for local lesion, and node and bone metastases were 91.7% vs. 41.7%, 92.0% vs. 32.0%, and 94.8% vs. 83.0% (p=0.041, p=0.0030, p<0.0001), respectively. 11C-choline-PET/CT is more useful for the staging and restaging of prostate cancer than FDG-PET/CT in Japanese men.

Diagnostic performance of 11C-choline PET/CT and bone scintigraphy in the detection of bone metastases in patients with prostate cancer.

The aim of this study was to compare 11C-choline PET/CT and bone scintigraphy (BS) for detection of bone metastases in patients with prostate cancer. Twenty-one patients with histologically proven prostate cancer underwent 11C-choline PET/CT and BS before (n = 4) or after (n = 17) treatment. Patient-, region-, and lesion-based diagnostic performances of bone metastasis of both 11C-choline PET/CT and BS were evaluated using a five-point scale by two experienced readers. Bone metastases were present in 11 (52.4%) of 21 patients and 48 (32.7%) of 147 regions; 111 lesions were found to have bone metastases. Region-based analysis showed that the sensitivity, specificity, accuracy, and area under the receiver-operating-characteristic curves (AUC) of 11C-choline PET/CT were 97.9%, 99.0%, 98.6%, and 0.9989, respectively; those of BS were 72.9%, 99.0%, 90.5%, and 0.8386, respectively. Sensitivity, accuracy, and AUC significantly differed between the two methods (McNemar test, p = 0.0015, p = 0.0015, and p < 0.0001, respectively). 11C-choline PET/CT detected 110/111 metastatic lesions (99.1%); BS detected 85 (76.6%) (p < 0.0001). According to the CT morphological type, the visualization rates of 11C-choline-PET/BS were 100%/90.3% for the blastic type, 91.7%/8.3% for the lytic type, 100%/100% for the mixed type, and 100%/53.3% for the invisible type, respectively. Significant differences in blastic, lytic, and invisible types were observed between the two methods (p = 0.013, p = 0.0044, and p = 0.023, respectively). In conclusion, 11C-choline PET/CT had greater sensitivity and accuracy than BS for detection of bone involvement in patients with prostate cancer.

11C-Choline positive but 18F-FDG negative pancreatic metastasis from renal cell carcinoma on PET.

Choline is a new PET tracer, which uptake may occur via a choline-specific transporter protein and be accelerated during the proliferation of tumor cells. We report a 61-year-old woman with a metastatic pancreatic tumor from renal cell carcinoma, measuring 35×40 mm. PET scans demonstrated accumulation of 11C-choline in the metastatic pancreatic tumor, but no accumulation of 18F-FDG. Choline PET/CT may play a useful and complementary imaging modality, especially when FDG-PET/CT does not show expected findings or when the evaluation of tumor viability is needed, in patients with renal cell carcinoma.

Prognostic value of pretreatment volume-based quantitative 18F-FDG PET/CT parameters in patients with malignant pleural mesothelioma.

PURPOSE: To investigate the relationships between pretreatment volume-based quantitative 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) parameters and overall survival (OS) in patients with malignant pleural mesothelioma (MPM). MATERIALS AND METHODS: We retrospectively reviewed data from 201 MPM patients, of whom 38 underwent surgical resection, and calculated the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), including primary tumors and nodal or distant metastatic lesions, on pretreatment 18F-FDG PET/CT. Relationships between clinicopathological factors (age, sex, performance status, European Organization for Research and Treatment of Cancer [EORTC] score, histological subtype, TNM stage, and treatment strategy), volume-based quantitative PET/CT parameters, and OS were evaluated using a Cox proportional hazards model and log-rank test. RESULTS: The median follow-up was 15 months (range, 1-96 months; median, 17 months). In a univariate analysis of all patients, older age (p<0.05), high EORTC score (p<0.001), non-epithelioid histological subtype (p<0.001), high T stage (p<0.001), positive N/M status (p<0.05, p<0.001), advanced TNM stage (p<0.001), non-surgical treatment (p<0.001), and high SUVmax (p<0.001), MTV (p<0.001), or TLG (p<0.001) were associated with significantly shorter OS. A multivariate analysis confirmed non-epithelioid subtype (hazard ratio [HR]: 1.69, 95% confidence interval [CI]: 1.14-2.48; p<0.05), non-surgical treatment (HR: 0.58, 95% CI: 0.34-0.95; p<0.05), and high TLG (HR: 1.97, 95% CI: 1.14-3.44; p<0.05) as independent negative predictors. CONCLUSIONS: Pretreatment volume-based quantitative 18F-FDG PET/CT parameters, especially TLG, could serve as potential surrogate markers for MPM prognosis.

11C-Choline-Avid but 18F-FDG-Nonavid Prostate Cancer with Lymph Node Metastases on Positron Emission Tomography.

Choline is a new positron emission tomography (PET) tracer useful for detection of prostate cancer and metastatic lesions. We report a 70-year-old man with prostate cancer and multiple abdominal, pelvic, and inguinal node metastases. PET scans demonstrated accumulation of 11C-choline in the primary tumor and lymph node metastases but no accumulation of 18F-FDG. Choline PET/computed tomography may be useful for diagnosis of advanced prostate cancer with suspected metastatic lesions and treatment planning.

Prognostic significance of preoperative 18F-FDG PET/CT for breast cancer subtypes.

Adjuvant treatments for operable breast cancers are determined according to subtypes defined based on estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status. The ER+/HER2- subtype can be divided into luminal A and luminal B usually by Ki67 expression levels. Although tumor size, lymph node metastasis and tumor grade have been widely accepted in daily clinical practice, the identification of further prognostic indicators especially in the ER+/HER2- subtype is warranted. A total of 387 operated breast cancers for which maximum standardized uptake value (SUVmax) on the 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) were available at baseline were retrospectively analyzed. The optimal cutoff value of SUVmax for relapse-free survival (RFS) was determined to be 3.585 by means of the receiver operating characteristics curve with an area under the curve of 0.6795 (95% CI: 0.5972 to 0.7618, p = 0.0006, sensitivity: 78.8%, specificity: 57.1%). The RFS of patients with SUVmax-high (n = 178) was significantly (p = 0.0003) worse compared with those with SUVmax-low (n = 209). This significant association was prominently recognized in the ER+/HER2- subtype. By multivariable analysis, SUVmax (hazard ratio: 3.83, 95% confidence interval: 1.28-11.51, p = 0.017), tumor size (4.22, 1.39-12.82, p = 0.011) and lymph node metastasis (4.44, 1.81-10.87, p = 0.0012) were significant and independent prognostic factors for RFS. The ER+/HER2- subtype demonstrated consistently worse RFS in the SUVmax-high patients both in the luminal A (p = 0.037) and luminal B (p = 0.047) subtypes. Combination of Ki67 and SUVmax appears to be useful for selecting patients who have inferior prognosis and need further adjuvant treatment of the ER+/HER2- subtype.

Correlation of the SUVmax of FDG-PET and ADC values of diffusion-weighted MR imaging with pathologic prognostic factors in breast carcinoma.

PURPOSE: To correlate both primary lesion maximum standardized uptake values (SUVmax) of FDG-PET/CT, and apparent diffusion coefficient (ADC) values of diffusion-weighted imaging (DWI) with clinicopathologic prognostic factors in patients with breast carcinoma. MATERIALS AND METHODS: 214 patients with 216 mass-type invasive breast carcinomas underwent whole-body FDG-PET/CT and 3-Tesla breast MRI including DWI before initial therapy. The primary tumor's SUVmax and ADC values were measured using FDG-PET/CT and DWI, respectively. Histologic analysis parameters included tumor size, expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67, nuclear grade, histology subtype, and axillary lymph node (LN) metastasis. The relationships among SUVmax, ADC values, and pathologic prognostic factors were evaluated. RESULTS: The mean SUVmax and ADCmean were 5.63±3.79 (range, 1.2-24.17) and 894±204×10(-6)mm(2)/s (range, 452-1550×10(-6)), respectively. There was a significant but weak inverse correlation between the SUVmax and ADCmean values (correlation coefficient r=-0.30, p<0.0001). SUVmax was associated with numerous prognostic factors such as tumor size (p<0.0001), expression levels of ER (p=0.00041), PR (p=0.00028), HER2 (p=0.00021), and Ki-67 (p<0.0001), nuclear grade (p<0.0001), histology subtype (p=0.00061), axillary LN metastasis (p<0.0001), and TNM staging (p<0.0001). Meanwhile, ADCmean value was associated with tumor size (p=0.013), expression of Ki-67 (p=0.0010), histology subtype (p=0.00013), axillary LN metastasis (p=0.00059), and TNM staging (p=0.0011). CONCLUSIONS: Primary tumor SUVmax on FDG-PET/CT has a stronger relationship with known prognostic parameters and may be a more useful for predicting the prognosis of breast carcinoma than ADC values.

Added value of pretreatment (18)F-FDG PET/CT for staging of advanced gastric cancer: Comparison with contrast-enhanced MDCT.

PURPOSE: To evaluate the added clinical value of pretreatment (18)F-FDG PET/CT compared with conventional contrast-enhanced multidetector-row CT (CECT) alone for staging of advanced gastric cancer MATERIALS AND METHODS: We studied 106 patients with locally advanced gastric cancer who underwent pretreatment CECT and (18)F-FDG PET/CT. Two experienced reviewers assessed the diagnostic performance of both CECT alone and the combination of CECT and (18)F-FDG PET/CT for the primary tumor, regional lymph node metastasis (N) and distant metastasis (M), rating their diagnostic confidence with a 5-point scoring system for each location. The two methods were compared using receiver operating characteristic (ROC) curve analysis for histopathologic findings, imaging, and clinical follow-up as the reference standards. RESULTS: Among the 106 patients, 96 primary tumors (90.6%) were detected by CECT, while 101 (95.3%) were clearly identified by (18)F-FDG PET/CT (p=0.074). Patient-based areas under the ROC curves for CECT alone versus the combination of CECT and (18)F-FDG PET/CT for diagnosis of N stage, peritoneal dissemination, liver metastasis, distant lymph node metastasis, bone metastasis, metastasis at other sites and overall M stage were 0.787 vs. 0.858 (p=0.13), 0.866 vs. 0.878 (p=0.31), 0.998 vs. 1.0 (p=0.36), 0.744 vs. 0.865 (p=0.049), 0.786 vs. 0.998 (p=0.034), 0.944 vs. 0.984 (p=0.34), and 0.889 vs. 0.912 (p=0.21), respectively. The diagnostic performance of primary tumor detection and NM staging was not influenced by the histologic subtype. CONCLUSION: Adding (18)F-FDG PET/CT to CECT provides better diagnostic accuracy for detection of distant lymph node metastasis and bone metastasis in patients with untreated advanced gastric cancer.

Update on advances in molecular PET in urological oncology.

Integrated positron emission tomography/computed tomography (PET/CT) with 2-[(18)F]fluoro-2-deoxy-D-glucose ((18)F-FDG) has emerged as a powerful tool for the combined metabolic and anatomic evaluation of many cancers. In urological oncology, however, the use of (18)F-FDG has been limited by a generally low tumor uptake, and physiological excretion of FDG through the urinary system. (18)F-FDG PET/CT is useful when applied to specific indications in selected patients with urological malignancy. New radiotracers and positron emission tomography/magnetic resonance imaging (PET/MRI) are expected to further improve the performance of PET in uro-oncology.

FDG-PET/CT as a post-treatment restaging tool in urothelial carcinoma: Comparison with contrast-enhanced CT.

PURPOSE: To assess the clinical usefulness of FDG-PET/CT in the diagnosis of recurrent and metastatic urothelial carcinoma in comparison with contrast-enhanced CT. MATERIALS AND METHODS: Eighty-three patients who had undergone treatment for histopathologically proven urothelial carcinoma underwent whole-body FDG-PET/CT and contrast-enhanced CT for suspected recurrence within a time interval of two weeks. Patient-based analysis and lesion sites besides the urinary tract, as interpreted by two experienced readers, were compared between the two modalities using McNemar test. Lesion status was determined on the basis of histopathology, radiological imaging and clinical follow-up for longer than 6 months. RESULT: Patient-based analysis showed that the sensitivity, specificity, and accuracy of FDG-PET/CT were 97.4%, 93.3% and 95.2%, respectively, whereas those of contrast-enhanced CT were 86.8%, 93.3% and 90.4%, respectively. The sensitivity and accuracy of FDG-PET/CT were higher than contrast-enhanced CT without significant difference (p=0.13). The sensitivity of FDG-PET/CT for diagnosis of bone metastasis was significantly higher than that of contrast-enhanced CT (93.8% vs. 25%, p=0.0026). CONCLUSION: FDG-PET/CT is a more accurate modality than CT for assessment of recurrence outside the urinary tract in patients with urothelial carcinoma, especially for bone lesion. Cystoscopy, urine cytology, and FDG-PET/CT are complementary procedures and may have a definite management role.

SUVmax on FDG-PET is a predictor of prognosis in patients with maxillary sinus cancer.

PURPOSE: Our aim was to determine whether the maximum standardized uptake value (SUVmax) of the primary lesion demonstrated by [(18)F]-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is associated with the prognosis of maxillary sinus cancer. MATERIALS AND METHODS: The relationships of clinicopathological factors including age, T stage, N stage, histologic type, treatment strategy, and primary tumor SUVmax with progression-free (PFS) and overall (OS) survival were evaluated using the log-rank test and Cox method in 31 patients with maxillary sinus cancer before combined superselective intra-arterial chemotherapy using high-dose cisplatin with concurrent radiotherapy, or radiotherapy alone. RESULTS: The median duration of follow-up was 55.4 (range 9.7-72.6) months. PFS and OS of patients exhibiting a high SUVmax (≥16 and ≥17, respectively) for the primary tumor were significantly lower than those of patients for whom the primary tumor SUVmax was low (p = 0.0010 and p = 0.033, respectively). Multivariate analyses showed that T stage (p = 0.0049) and primary tumor SUVmax (p = 0.026) were independently prognostic of poorer PFS and that only primary tumor SUVmax (p = 0.049) was independently prognostic of poorer OS. CONCLUSION: SUVmax of the primary tumor determined by FDG-PET/CT before treatment could be a good surrogate marker for prognostication of maxillary sinus cancer.

Diagnostic and prognostic value of (18)F-FDG PET/CT for axillary lymph node staging in patients with breast cancer.

PURPOSE: To investigate the diagnostic and prognostic value of (18)F-FDG-PET/CT for axillary lymph node (LN) staging in breast cancer patients, employing histologic evaluation as the reference. METHODS: Among 196 patients with biopsy-proven breast cancer who had undergone (18)F-FDG-PET/CT before mastectomy or breast-conserving surgery with sentinel LN biopsy and/or axillary LN dissection, 200 axillae were retrospectively analyzed by visual assessment and quantitatively using SUVmax. LN SUVmax as well as other clinicopathological features were assessed for their prognostic value using the log-rank test and Cox method. RESULTS: Metastasis was diagnosed histopathologically in 56 (28 %) axillae. The sensitivity, specificity, and accuracy of visual PET/CT for diagnosing node metastasis were 55.4, 95.8, and 84.5 %, respectively. When the optimal discriminative SUVmax cutoff was 1.5, these figures were 51.8, 97.2, and 84.5 %, respectively. Fourteen of 55 patients (25.5 %) with LN metastases suffered a recurrence during follow-up (median 39 months). Patients with a high nodal SUVmax (≥1.7) had a significantly lower progression-free survival rate than those with a low SUVmax (p = 0.0499). Axillary nodal and primary tumor SUVmax as well as estrogen receptor status were significantly associated with recurrence. CONCLUSION: Axillary nodal SUVmax may be a prognostic indicator of disease recurrence in patients with axillary LN metastases.

Association between ¹8F-FDG uptake and molecular subtype of breast cancer.

PURPOSE: To determine whether (18)F-FDG uptake in breast cancer correlates with immunohistochemically defined subtype and is able to predict molecular subtypes. METHODS: This retrospective study involved 306 patients with 308 mass-type invasive breast cancers (mean size 2.65 cm, range 1.0-15.0 cm) who underwent (18)F-FDG PET/CT before therapy. The correlations between primary tumour (18)F-FDG uptake on PET/CT, expressed as SUVmax, and clinicopathological findings and molecular subtype, i.e. luminal A, luminal B (HER2-negative), luminal B (HER2-positive), HER2-positive and triple-negative, were analysed. The predictors of these subtypes were investigated. RESULTS: The mean SUVmax of the 308 tumours was 5.33 ± 3.63 (range 1.15-19.01). Among the subtypes of the 308 tumours, 87 (28.2 %) were luminal A, 111 (36.0 %) were luminal B (HER2-negative), 31 (10.1 %) were luminal B (HER2-positive), 26 (8.4 %) were HER2-positive and 53 (17.2 %) were triple-negative, and the corresponding mean SUVmax were 3.41 ± 2.07 (range 1.18-14.30), 5.17 ± 3.52 (range 1.35-19.01), 6.57 ± 3.84 (range 1.42-15.58), 7.55 ± 3.63 (range 2.30-13.60) and 6.97 ± 4.17 (range 1.15-16.06), respectively. A cut-off value of 3.60 yielded 70.1 % sensitivity and 66.1 % specificity with an area under the receiver operating characteristics curve (AUC) of 0.734 for predicting that a tumour was of the luminal A subtype. A cut-off value of 6.75 yielded 65.4 % sensitivity and 75.2 % specificity with an AUC of 0.704 for predicting a HER2-positive subtype. CONCLUSION: SUVmax, a metabolic semiquantitative parameter, shows a significant correlation with the molecular subtype of breast cancer, and is useful for predicting the luminal A or HER2-positive subtype.

Development of Fingertip Synchrotron Radiation Microangiography toward Clinical Prediction of Diabetic Microangiopathy.

OBJECTIVES: The spatial resolution of conventional angiographic systems is not enough to predict diabetic microangiopathy in arterioles (20-200 µm). METHODS: To determine whether fingertip synchrotron (SR) radiation microangiography has enough spatial resolution to quantitate arteriolar diameter changes, and whether an arteriolar paradoxical vasoconstriction is a characteristic observation for diabetic microangiopathy, diameter reduction as arteriolar branching and difference of the diameter changes induced by acetylcholine between control (n = 5) and diabetic rats (n = 5) were analyzed. RESULTS: Fingertip SR microangiography visualized the arterioles with a diameter range of 30-300 µm and demonstrated vascular diameter reduction as branching with a fixed ratio (r = 0.93, P < 0.004 and r = 0.73, P < 0.001). A vasodilatory reaction was induced by acetylcholine in the control (142.4 ± 61.9 to 190.9 ± 73.5, P < 0.05, n = 25), in contrast, paradoxical vasoconstriction in diabetic rats (201.6 ± 83.0 to 16 0.4 ± 67.9, P < 0.05, n = 37). Histological angiopathy was noted only in the diabetic rats. CONCLUSION: In conclusion, the fingertip SR microangiography is useful to predict diabetic micrangiopahty.

Quantification of myocardial blood flow using (201)Tl SPECT and population-based input function.

OBJECTIVES: Thallium-201 ((201)Tl) single photon emission computed tomography (SPECT) is an important tool in the diagnosis of ischemic heart disease. Absolute quantification of myocardial blood flow (MBF) has the potential to provide more useful information on myocardial perfusion than semi-quantitative assessments. This study aimed to validate the quantification of MBF using (201)Tl cardiac SPECT based on a population-averaged input function (STD-IF) and one-point blood sample technique. METHODS: (201)Tl emission and computed tomography (CT)-based attenuation scans were performed on 11 healthy volunteers at rest using a SPECT/CT scanner. Individual input functions (IND-IFs) during the emission scans were based on arterial blood samples. The STD-IF technique was validated as follows: (1) optimal time to calibrate a STD-IF was determined to minimize differences between the calibrated STD-IF and the IND-IFs. (2) Tissue time-activity curves (TTACs) were generated based on a single-tissue compartment model for MBFtrue = 0.5, 1.0, 1.5, and 2.0 mL/min/g, a constant distribution volume of 45 mL/mL, and IND-IFs. The pseudo STD-IF for each subject was generated using the leave-one-out technique. Using the optimal calibration time and the pseudo STD-IFs, MBF values were estimated on the TTACs with an autoradiography method. Optimal mid-scan time (MST) with a fixed duration of 20 min was determined to minimize intersubject variation in estimated MBF errors, and (3) Global and regional MBF values estimated with pseudo STD-IFs were compared to those with IND-IFs using the optimal calibration time and MST. RESULTS: The optimal calibration time and MST were both 20 min after (201)Tl injection. Global MBF determined using both IND-IFs and pseudo STD-IF showed significant correlations with rate-pressure products, R (2) = 0.645; p < 0.01 and R (2) = 0.303; p < 0.05, respectively. The mean percent error in regional MBF using pseudo STD-IFs was 0.69 ± 7.80 % (-12.80 to 14.25 %). No significant difference was observed between regional MBF values using IND-IFs and pseudo STD-IFs. CONCLUSION: This study demonstrated that the proposed technique based on a STD-IF and one-point blood sample provided hemodynamically reasonable global MBF values and the regional MBF values comparable to those with IND-IFs.

Cerebral blood flow and metabolism of hyperperfusion after cerebral revascularization in patients with moyamoya disease.

In moyamoya disease (MMD), surgical revascularization may be complicated with postoperative hyperperfusion. We analyzed cerebral perfusion and metabolism using positron emission tomography (PET) or single-photon emission computed tomography (SPECT) before and after bypass surgery on 42 sides of 34 adult patients with MMD. In seven cases (16.7%) with symptomatic hyperperfusion, diagnosed by qualitative (123)I-iodoamphetamine (IMP) SPECT, a subsequent PET study during postoperative subacute stages revealed significantly increased cerebral blood flow (CBF) from 34.1 ± 8.2 to 74.3 ± 12.8 mL/100 g per minute (P<0.01), a persistent increase in cerebral blood volume (CBV) from 5.77 ± 1.67 to 7.01 ± 1.44 mL/100 g and a significant decrease in oxygen extraction fraction (OEF) from 0.61 ± 0.09 to 0.40 ± 0.08 (P<0.01). Mean absolute CBF values during symptomatic hyperperfusion were more than the normal control +2 standard deviations, the predefined criteria of PET. Interestingly, two patients with markedly increased cerebral metabolic rate of oxygen (CMRO(2)) at hyperperfusion were complicated with postoperative seizure. Among preoperative PET parameters, increased OEF was the only significant risk factor for symptomatic hyperperfusion (P<0.05). This study revealed that symptomatic hyperperfusion in MMD is characterized by temporary increases in CBF >100% over preoperative values caused by prolonged recovery of increased CBV.

Preserved acetazolamide reactivity in lacunar patients with severe white-matter lesions: 15O-labeled gas and H2O positron emission tomography studies.

Limited evidence exists on the relationships between severity of white-matter lesions (WMLs) and cerebral hemodynamics in patients without major cerebral artery disease. To examine changes of cerebral blood flow (CBF), oxygen metabolism, and vascular reserve capacity associated with severity of WML in patients with lacunar stroke, we used a positron emission tomography (PET). Eighteen lacunar patients were divided into two groups according to the severity of WMLs, assessed by Fazekas classification; grades 0 to 1 as mild WML group and grades 2 to 3 as severe WML group. Rapid dual autoradiography was performed with (15)O-labeled gas-PET followed by (15)O-labeled water-PET with acetazolamide (ACZ) challenge. Compared with the mild WML group, the severe WML group showed lower CBF (20.6±4.4 versus 29.9±8.2 mL/100 g per minute, P=0.008), higher oxygen extraction fraction (OEF) (55.2±7.4 versus 46.7±5.3%, P=0.013), and lower cerebral metabolic rate of oxygen (CMRO(2)) (1.95±0.41 versus 2.44±0.42 mL/100 g per minute, P=0.025) in the centrum semiovale. There were no significant differences in the ACZ reactivity between the two groups (48.6±22.6% versus 42.5±17.2%, P=0.524). Lacunar patients with severe WMLs exhibited reduced CBF and CMRO(2), and increased OEF in the centrum semiovale. The ACZ reactivity was preserved in both patients with severe and mild WMLs in each site of the brain.