Long-lasting complete remission in a patient with systemic metastases of recurrent breast cancer treated with cyclin-dependent kinases 4/6 inhibitors: a case report.

BACKGROUND: The prognosis for recurrence cases of hormone receptor-positive HER2-negative breast cancer remains poor, and treatment strategies that emphasize quality of life have often been chosen, with few physicians aiming for a cure. Our objective is to assess the validity of such current treatment strategies. CASE PRESENTATION: A 74-year-old Asian woman with multiple lung and liver metastases after local recurrence of breast cancer was treated with two different cyclin-dependent kinases 4/6 inhibitors sequentially in combination with endocrine therapy. Flow cytometric analysis of the patient's peripheral blood mononuclear cells was also performed to evaluate the host's immune status. Complete remission was achieved without cytotoxic agents and the patient remains disease free to this day, 6 years after the initial relapse. Additionally, no increase in the population of the immunosenescent T cells with a phenotype of CD8+CD28- was observed in the patient's peripheral blood mononuclear cells, suggesting that the immune system was well maintained. CONCLUSIONS: We present this case study to develop new treatment strategies for recurrent breast cancer that is not only bound to misinterpretations of the Hortobagyi algorithm, but also aim for a cure with noncytotoxic agents to maintain the host's immune system and early detection of recurrence.

A patient with stage IIIB advanced breast cancer who is still alive 24 years after surgery: a case report and remarks on the treatment strategies.

Background: In recent years, a number of agents possessing novel mechanisms, such as cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors and PIK3CA inhibitors, have been developed for the treatment of hormone receptor-positive (HR+) human epidermal growth factor receptor type negative (HER2-) advanced or recurrent breast cancer. As a result, the treatment strategies for advanced or recurrent breast cancer have changed significantly. The combination of CDK 4/6 inhibitors administration and endocrine therapy is now widely used in the treatment of HR+ HER2- recurrent breast cancer with improved outcomes. In 2021, abemaciclib was approved as post-operative adjuvant combination therapy with endocrine therapy for HR+ HER2- advanced breast cancer and is expected to suppress postoperative recurrence. A range of new agents are being developed in addition to CDK4/6 inhibitors that provided more options of treatment strategies for advanced or recurrent breast cancer, which in turn could improve outcomes. However, the prognosis for the recurrent HR+ HER2- breast cancer remains poor, overall survival (OS) is still very low and a complete cure is difficult even with the treatments. Case Description: In 1998, 24 years ago, neoadjuvant chemotherapy (NAC) and the concept of subtypes were not even widespread, the number of available drugs was far fewer than today, the clinical treatment guidelines had not been established. Nevertheless, we experienced a case of HR+ HER2- advanced breast cancer, stage IIIB at the initial diagnosis, which was consistently treated with the aim of complete cure and with the various treatments available at the time, resulting in long-term survival. 24 years have passed since the initial surgery, the patient has continued to do well despite repeated recurrences and remissions. Conclusions: We report here a case of long-term survival in advanced breast cancer of 24 years after surgery, and remark for future treatment strategies that not bound by the conventional treatment policy that emphasizes quality of life without aiming for complete cure.

Case report: two cases of extremely rare primary pure squamous cell carcinoma of the breast.

RATIONALE: Since primary pure squamous cell carcinoma of the breast is a rare disease, few reports describe the characteristic findings on performing preoperative imaging that can be used to distinguish it from normal breast cancer. The rapid evolution and lack of an established method of treatment has resulted in several reports of advanced cases of primary pure squamous cell carcinoma of the breast. PATIENT CONCERNS: Case 1 was a 44-year-old woman with an elastic, hard tumor in the left C region. Ultrasonographic analysis revealed a maximal 11-mm hypoechoic area. Histologically, the tumor was a well-differentiated squamous cell carcinoma with prominent keratinization, and there was prominent inflammatory cell infiltration, necrosis, and fibrosis. Case 2 was a 58-year-old woman with an elastic, hard tumor in the left C/D region. Ultrasonographic analysis revealed a maximal 31-mm hypoechoic area with partially calcified areas and a hyperechoic margin. Histologically, the tumor was a squamous cell carcinoma with prominent keratinization exhibiting an infiltrative growth pattern. The tumor had no connection to the epidermis and partially transitioned into the atypical ductal epithelium in the area surrounding the focus. DIAGNOSES: The patient in Case 1 was preoperatively diagnosed with T1cN0M0 Stage I cancer of the left breast, but both patients were finally diagnosed with T2N0M0 Stage IIA cancer. INTERVENTIONS: Case 1: left partial mastectomy and axillary lymph node dissection were performed. The patient was administered 4 courses of FEC100 and 4 courses of DTX as postoperative adjuvant therapy. Case 2: left modified radical mastectomy and axillary lymph node dissection were performed without any postoperative adjuvant therapy. OUTCOMES: Case 1: no sign of relapse was observed, but the patient moved away from the area to another hospital in March 2014 and eventually died due to relapse in January 2016. Case 2: four years after surgery, no relapse has been observed. LESSONS: We should always keep the presence of primary pure squamous cell carcinoma among breast cancers in mind although the crisis rate is very low. Due to its high malignancy, needle biopsy and aspiration biopsy cytology should be performed to make a definitive diagnosis.

Spin-crossover behavior and electrical conduction property in iron(II) complexes with tetrathiafulvalene moieties.

Iron(II) complexes with neutral and oxidized tetrathiafulvalene (TTF) moieties were prepared and X-ray crystallographic analyses, magnetic and electrical resistivity measurements suggested an interaction of spin transition and electrical conductivity.

Rational approach to the synthesis, evaluation, and (68)ga labeling of a novel 4-anilinoquinoline epidermal growth factor receptor inhibitor as a new imaging agent that selectively targets the epidermal growth factor receptor tyrosine kinase.

Certain small-molecule inhibitors that target epidermal growth factor receptor (EGFR), such as Gefitinib, Erlotinib, and Lapatinib, provide a new approach for cancer treatment. In accordance with the pharmacophore model for inhibitor competition at EGFR-binding site, this study proposes a rationalized design for a novel 4-anilinoquinoline EGFR tyrosine kinase inhibitor, [6,7-dimethoxyethoxy]-quinolin-4-yl]-(3-ethynylphenyl)-amine (YCU07). This is the first study to apply ring-closing metathesis toward synthesis of the quinoline nucleus for this 4-anilinoquinoline EGFR inhibitor. YCU07 expressed significant inhibitory activity for EGFR tyrosine kinase in A431 cells, as confirmed by an ABTS microwell peroxidase substrate system read colorimetrically at 405 nm. Injection of (68)Ga-labeled glutamic acid polypeptide (GAP)-YCU07 conjugate in nude mice implanted with A431 was imaged by animal PET camera (LabPET8; Gamma Medica-Ideas) and computed tomography (eXplore Locus; GE Healthcare), to evaluate its biodistribution. (68)Ga-GAP-YCU accumulated in the receptor-positive tumors, with uptake values of 1.50% +/- 0.09% and 2.36% +/- 0.36% of injected activity per gram tissue at 30 and 90 minutes, respectively.

Multiple bistability and tristability with dual spin-state conversions in [Fe(dpp)2][Ni(mnt)2]2 x MeNO2.

The multicomponent system of [Fe(dpp)(2)][Ni(mnt)(2)](2).MeNO(2) (1; dpp = 2,6-bis(pyrazol-1-yl)pyridine and mnt = maleonitriledithiolate) was prepared by the reaction of [Fe(dpp)(2)](BF(4))(2) with (Bu(4)N)[Ni(mnt)(2)] in MeNO(2). Variable-temperature X-ray structural analyses, magnetic susceptibility, and heat capacity measurements confirmed that 1 undergoes multiple spin-state conversions in both the cationic and anionic components. The asymmetric unit in the crystal contains one [Fe(dpp)(2)](2+) cation, two [Ni(mnt)(2)](-) anions ([Ni1](-) and [Ni2](-)), and one solvent molecule. Magnetic susceptibility measurements revealed that a paramagnetic state in the high-temperature region (HT phase) was abruptly converted to a diamagnetic low-temperature (LT) phase below 180 K as the temperature was lowered from 270 K. As the temperature was raised from 125 to 270 K, successive phase transitions occurred to the HT phase via intermediate phases (IM1, IM2, and IM3) at 175.5, 186.5, 194.0, and 244.0 K, respectively. In the HT phase [Fe(dpp)(2)](2+) is in the high-spin state, and each [Ni1](-) and [Ni2](-) moiety is arranged in monomeric form with an S = (1)/(2) spin ground state. In the LT phase [Fe(dpp)(2)](2+) is in the low-spin state and the nickel moieties are dimerized and diamagnetic. In the IM1 and IM2 phases the iron(II) sites are partially in the HS state and both [Ni](-) moieties are dimeric, as suggested by (57)Fe Mossbauer measurements. In the IM3 phase, [Fe(dpp)(2)](2+) is in the HS state and the anions exist in both their monomeric ([Ni1](-)) and dimeric ([Ni2](-)) forms. Rapid thermal quenching from 300 to 5 K yielded a metastable HS phase, which relaxed to the LT phase via the IM1 phase as the temperature was raised to 150 K. A partial light induced spin transition on the iron site was observed at 5 K.

Combining chronic kidney disease with 201thallium/123iodine beta methyliodophenyl pentadecanoic acid dual myocardial single-photon emission computed tomography findings is useful for the evaluation of cardiac event risk.

OBJECTIVE: Chronic kidney disease is a noteworthy pathophysiology as a risk factor of cardiovascular disease. We investigated the usefulness of combining glomerular filtration rate and 201thallium(201TI)/123iodine-beta-methyliodophenyl pentadecanoic acid (123I-BMIPP) dual myocardial scintigraphic findings for predicting cardiac events. METHODS: Seventy-five patients suspected of coronary artery disease underwent 201TI/123I-BMIPP dual myocardial scintigraphy. Clinical and nuclear variables were included in the multivariate analysis for predicting hard events (cardiac death and nonfatal myocardial infarction) and soft events (unstable angina, heart failure, and coronary revascularization). Glomerular filtration rate was estimated by the modification of diet in renal disease formula. Kaplan-Meier analysis was performed to investigate the incremental prognostic value of glomerular filtration rate. RESULTS: During the mean follow-up period of 425 days, eight patients had hard events and 20 patients had soft events. Multivariate analysis revealed that glomerular filtration rate and the sum of total defect score in 123I-BMIPP image were independent predictors of total cardiac events, whereas sex, diabetes, glomerular filtration rate, and the number of abnormal segments in 201TI image were those of hard events. Kaplan-Meier analysis revealed that greater risk stratification was achieved by adding a glomerular filtration rate of lesser than 60 ml/min/1.73 m2 to the sum of the total defect score > or = 5 in the 123I-BMIPP image. Greater risk stratification for hard events was also achieved by adding a glomerular filtration rate of lesser than 30 ml/min/1.73 m2 to the number of abnormal segments > or = 2 in 201TI image. CONCLUSION: Better risk stratification can be achieved by adding glomerular filtration rate to 201TI/123I-BMIPP dual myocardial scintigraphic findings.

Total Mini-Mental State Examination score and regional cerebral blood flow using Z score imaging and automated ROI analysis software in subjects with memory impairment.

OBJECTIVE: The Mini-Mental State Examination (MMSE) is considered a useful supplementary method to diagnose dementia and evaluate the severity of cognitive disturbance. However, the region of the cerebrum that correlates with the MMSE score is not clear. Recently, a new method was developed to analyze regional cerebral blood flow (rCBF) using a Z score imaging system (eZIS). This system shows changes of rCBF when compared with a normal database. In addition, a three-dimensional stereotaxic region of interest (ROI) template (3DSRT), fully automated ROI analysis software was developed. The objective of this study was to investigate the correlation between rCBF changes and total MMSE score using these new methods. METHODS: The association between total MMSE score and rCBF changes was investigated in 24 patients (mean age +/- SD 71.5 +/- 9.2 years; 6 men and 18 women) with memory impairment using eZIS and 3DSRT. Step-wise multiple regression analysis was used for multivariate analysis, with the total MMSE score as the dependent variable and rCBF change in 24 areas as the independent variable. RESULTS: Total MMSE score was significantly correlated only with the reduction of left hippocampal perfusion but not with right (P < 0.01). CONCLUSIONS: Total MMSE score is an important indicator of left hippocampal function.

Fluorine-18-labeled 5-fluorouracil is a useful radiotracer for differentiation of malignant tumors from inflammatory lesions.

OBJECTIVE: [(18)F]-2-fluoro-2-deoxy-D-glucose ([(18)F]-FDG) is a useful radiotracer to detect malignant tumors. However, inflammatory processes are likely to be mistaken as malignant tumors owing to strong accumulation of [(18)F]-FDG. The fluorinated nucleoside base 5-fluorouracil has remained an important antimetabolite agent in the treatment of a variety of cancers. The objective of this study was to evaluate the possibility of discriminating between malignant tumors and inflammation by [(18)F]-5-fluorouracil ([(18)F]-5-FU). METHODS: [(18)F]-5-FU was made with >95% radiochemical purity in our laboratory. BALB/cAJcl-nu/nu mice were subcutaneously inoculated with colon carcinoma cell line, colon 26, into the left side of the back and turpentine oil into the right side of the back to cause chemical inflammation. We examined the biodistribution of [(18)F]-5-FU in control mice and tumor-inflammation mice. We also examined the biodistribution of [(18)F]-FDG as a baseline study. Approximately 1 MBq of either [(18)F]-5-FU or [(18)F]-FDG was injected into the tail vein of each mouse. The biodistribution study was performed at 1 and 2 h after injection. The radioactivity of each organ was measured by a gamma counter. RESULTS: [(18)F]-5-FU uptakes in the liver and the kidney were especially high. Tumor-to-blood ratios were significantly higher at 2 h than at 1 h (3.69 +/- 0.40 vs. 1.81 +/- 0.37, P < 0.001). Tumor-to-inflammation ratios at 2 h following injection were significantly higher than those at 1 h (1.94 +/- 0.44 vs. 1.26 +/- 0.20, P < 0.001). At 2 h after radiotracer injection, the tumor-to-inflammation ratio of [(18)F]-5-FU was significantly higher than that of [(18)F]-FDG (1.94 +/- 0.44 vs. 1.03 +/- 0.23, P = 0.001). CONCLUSIONS: Our data suggest that [(18)F]-5-FU has a diagnostic potential as a positron emission tomography ligand for differentiating malignant tumors from inflammatory lesions.

SUV correction for injection errors in FDG-PET examination.

OBJECTIVE: Many studies have documented the clinical usefulness of standardized uptake values (SUV) for diagnosis. However, in the event of injection error, accurate measurements cannot be obtained if the radioactivity of fluorodeoxyglucose (FDG) leakage is not subtracted from the administered dosage. Here, a correction formula for radioactivity estimation that takes into account the radioactivity of FDG leakage was derived on the basis of a phantom experiment. Furthermore, to determine whether SUV could be accurately calculated by the correction formula, we performed a volunteer study. METHODS: Images were displayed by altering the conversion constant from 1.0, 0.1 to 0.01, and the range of correctable counts was verified on the basis of image inversion. To estimate the radioactivity of FDG leakage by imaging, the count of the leakage was measured, converted into a radioactivity concentration using a cross-calibration factor (CCF), and multiplied by volume, as measured by imaging. Three factors that markedly affect count, i.e., count rate performance, partial volume effect and crosstalk, were assessed in phantom studies in order to derive a correction formula. In addition, to clarify the accuracy of the correction formula, we attached to the right elbow. RESULTS: With a conversion constant of 0.1, there was no image inversion at or=28 mm Leakage radioactivity (MBq)=positron emission tomography (PET) radioactivity (MBq)x0.9. For leakages of >or=15 mm but <28 mm Leakage radioactivity (MBq)=PET radioactivity (MBq)x0.9x(0.0517xleakage size (mm)-0.4029). In a volunteer study with 10 MBq leakage, SUV recalculated using the formula achieved 99.97% correction, whereas with 100 MBq leakage, SUV achieved 67.5% resulting in poor correction. CONCLUSIONS: The present correction technique can accurately calculate SUV and could be useful for the clinical diagnosis of malignant tumors.

Functional imaging of estrogen receptors with radiolabeled-GAP-EDL in rabbit endometriosis model.

RATIONALE AND OBJECTIVES: Endometriosis is a common women's health problem. Animal models provide an invaluable tool to study the natural history of endometriosis. We previously have reported that (99m)Tc-labeled glutamate peptide-estradiol ((99m)Tc-GAP-EDL) is a useful agent for imaging functional estrogen receptor (ER) via an ER-mediated process. This study was to evaluate the feasibility of using radiolabeled GAP-EDL to image ER-positive (ER +) endometriosis in nonprimate animal models. MATERIALS AND METHODS: 3-Aminoethyl estradiol (EDL) was conjugated to glutamate peptide (GAP) to yield GAP-EDL. In vitro cellular uptake studies of (99m)Tc and (68)Ga-GAP-EDL inhibition with cold estrone were conducted in 13,762 rat mammary tumor cells. To create a rabbit model with endometriosis, part of uterine tissue was dissected and grafted in the peritoneal wall. Eight weeks after surgery, scintigraphic images were obtained after intravenous injection of (99m)Tc-GAP-EDL (1 mCi/rabbit, intravenous) at 0.5-2.0 hours, and (68)Ga-GAP-EDL at 45 minutes. We also performed (68)Ga-GAP-EDL blocking study in rabbit model by using tamoxifen. The rabbits were sacrificed and the grafts were excised for histologic examination. RESULTS: In vitro uptake study of (99m)Tc- and (68)Ga-GAP-EDL in 13,762 rat breast cancer cells showed gradually increasing uptake of both tracers. Accumulation of (68)Ga-GAP-EDL in 13,762 cells was inhibited with cold estrone in a dose-dependent manner. In the endometriosis model, the grafted uterine tissue could be visualized by (99m)Tc-GAP-EDL. Necropsy was performed at 2.5 hours after injection time. Four follicular endometrial lesions in eight implanted endometrial tissues were detected, and all lesions could be detected by (99m)Tc-GAP-EDL. Planar scintigraphy of uterus, ovary and implants of necropsy specimen revealed an increased uptake of (99m)Tc-GAP-EDL in comparison with surrounding abdominal wall tissue. Microscopic examinations support that (99m)Tc-GAP-EDL was accumulated in the microinvasive endometrial tissue. After blocking with tamoxifen, (68)Ga-GAP-EDL accumulation in the endometrial grafts could not be visualized, and endometrial tissue-to-normal tissue count ratios were statistically higher in a nonblocked image than that in the blocked image. CONCLUSIONS: Endometriosis uptake of radiolabeled GAP-EDL was via an estrogen receptor-mediated process. Radiolabeled-GAP-EDLs are useful agents for imaging endometriosis.

Inter-observer variations in FDG-PET interpretation for cancer screening.

BACKGROUND: Diagnostic guidelines for the use of 2-(fluorine 18) fluoro-2 deoxy-D-glucose (FDG)-positron emission tomography (PET) in cancer screening have yet to be established. We assessed inter-observer variability in screening FDG-PET. METHODS: Subjects comprised 40 individuals who underwent FDG-PET and computed tomography (CT) for cancer screening. To assess various patterns of FDG uptakes, three subsets of the cases were selected: 'Cancer', 15 cases with cancer; 'Not malignant', 15 cases with suspected cancer by FDG-PET who were confirmed as cancer-free; and 'Normal', 10 cases without remarkable FDG uptake who were confirmed as cancer-free. A total of 68 lesions made up of malignancy (n = 18), benign (n = 21), and physiological FDG uptake (n = 29) were interpreted by six physicians. Each observer reviewed each case three times. Step 1 involved interpretation of PET images alone, Step 2 involved side-by-side reading of PET and CT images, and Step 3 involved re-evaluation of findings with the results of other screening tests. We assessed inter-observer agreement for each step. RESULTS: Inter-observer agreement for all lesions at each step was moderate, compared to fair agreement for 'Normal' subjects. Inter-observer agreement of 'Cancer' and 'Not malignant' subjects in Step 1 were better than those in Step 2 and 3; however, the differences were not statistically significant. CONCLUSION: The interpretation of FDG-PET is adequately reproducible, while that of 'Normal' subjects is less reproducible. Improvement of inter-observer variability in assessing physiological FDG uptakes requires universal reporting criteria in FDG-PET. Correlative interpretation of PET, CT and other information may require standardization in subjects with suspected cancer by FDG-PET.

FDG-PET of patients with suspected renal failure: standardized uptake values in normal tissues.

OBJECTIVE: This study aims to clarify the effect of renal function on 2-[(18)F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) imaging and determine the clinical significance of renal function in this setting. We compared FDG distribution between normal volunteers and patients with suspected renal failure. METHODS: Twenty healthy volunteers and 20 patients with suspected renal failure who underwent FDG-PET between November 2002 and May 2005 were selected for this study. We define "patients with suspected renal failure" as having a blood serum creatinine level in excess of 1.1 mg/dl. The serum creatinine level was examined once in 2 weeks of the FDG-PET study. Regions of interest were placed over 15 regions for semi-quantitative analysis: the white matter, cortex, both upper lung fields, both middle lung fields, both lower lung fields, mediastinum, myocardium of the left ventricle, the left atrium as a cardiac blood pool, central region of the right lobe of the liver, left kidney, and both femoris muscles. RESULTS: The mean standardized uptake values (SUVs) of brain cortex and white matter were higher in healthy volunteers than in renal patients. The mean SUVs of the mediastinum at the level of the aortic arch and left atrium as a cardiac blood pool were lower in healthy volunteers than in patients with suspected renal failure. These regions differed between healthy volunteers and patients with suspected renal failure (P < 0.05). CONCLUSIONS: We found decreasing brain accumulation and increasing blood pool accumulation of FDG in patients with high plasma creatinine. Although the difference is small, this phenomenon will not have a huge effect on the assessment of FDG-PET imaging in patients with suspected renal failure.

Clinical evaluation of the effect of attenuation correction technique on 18F-fluoride PET images.

OBJECTIVE: The purpose of this study is to evaluate effect of attenuation correction technique on 18F-fluoride positron emission tomography (PET). METHODS: We performed PET scans after the injection of 185 MBq 18F-fluoride on 32 patients from October 20th, 2004 to April 13th, 2005. We calculated bone-to-muscle ratios for the images with and without attenuation correction. We placed regions of interest (ROIs) on normal bone accumulation in 22 patients. The exclusion criteria were bone metastasis, Paget's disease, and rheumatoid arthritis. Several regions were chosen for ROI placement: skull, cervical vertebra, mandible, scapula, thoracic vertebra, rib, humerus, lumbar vertebra, radius, ulna, pelvis, femoral head, femoral shaft, tibia, and fibula. The count ratios of normal bones to gluteus muscle were calculated as bone-to-muscle ratios. The count ratios of abnormal skeletal lesions to gluteus muscles were calculated as bone-to-muscle ratios, while the count ratios of abnormal skeletal lesions to normal bones were calculated as bone-to-bone ratios. RESULTS: PET images without attenuation correction showed significantly higher mean bone-to-muscle ratios than those with attenuation correction (p < 0.05) for all normal bones except the femoral head and lumbar vertebrae. For abnormal bones, bone-to-muscle ratios without attenuation correction were significantly higher than those with attenuation correction (p < 0.005). The same statistical significance was found for bone-to-bone ratios (p < 0.005). CONCLUSIONS: The attenuation correction technique is not necessary to conduct the visual interpretation of 18F-fluoride PET images. The bone-to-muscle ratio analysis without attenuation correction may be of use to differentiate malignant from benign disease processes.

Electrochemical transfer of (18)F from (18)O water to aprotic polar solvent.

Electrochemical transfer of (18)F(-) from enriched [(18)O]-water to pure acetonitrile was investigated to develop a simple and effective synthesis of (18)F-radiopharmaceuticals. The transfer of (18)F is composed of two steps: first step is electro-deposition on a graphite anode and the next step is electro-emission into pure acetonitrile by inversing the polarity of the electric tension. A sufficiently high fraction of the electro-emission, 73%, was achieved. The electrochemical transfer of (18)F to aprotic polar solvents without any additives, such as phase transfer catalysis, will make the synthesis of diverse (18)F-radiopharamceuticals simple and easy.

The roles of PET and PET/CT in the diagnosis and management of prostate cancer.

2-(18)F-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) imaging in prostate cancer is challenging because glucose utilization in well-differentiated prostate cancer is often lower than in other tumor types. Nonetheless, FDG-PET has a high positive predictive value for untreated metastases in viscera, but not lymph nodes. A positive FDG-PET can provide useful information to aid the clinician's decision on future management in selected patients who have low prostate-specific antigen levels and visceral changes as a result of metastases. On the other hand, FDG-PET is limited in the identification of prostate tumors, as normal urinary excretion of radioisotope can mask pathological uptake. Moreover, there is an overlap in the degree of uptake between prostate cancer, benign prostatic hyperplasia and inflammation. The tracer choice is also important. (11)C-choline has the advantage of reduced urinary excretion, and thus (11)C-choline PET may provide more accurate information on the localization of main primary prostate cancer lesions than MRI or MR spectroscopy. (11)C-choline PET is sensitive and accurate in the preoperative staging of pelvic lymph nodes in prostate cancer. A few studies are available but there were no PET or PET/CT studies with a large number of patients for tissue confirmation of prostate cancer; further investigations are required.

Reverse perfusion-metabolism mismatch predicts good prognosis in patients undergoing cardiac resynchronization therapy: a pilot study.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves glucose metabolism in the septum of patients with heart failure, so in the present study the predictive value of combined fluorodeoxyglucose (FDG)-positron emission tomography (PET) and metoxy-isobutyl isonitrile (MIBI)-single photon emission computed tomography (SPECT) for the prognosis of patients undergoing CRT was investigated. METHODS AND RESULTS: Fourteen patients (70.3+/-8.2 years) who underwent FDG-PET and MIBI-SPECT before implantation of a biventricular pacemaker were enrolled. The total number of matches, mismatches, reverse mismatches, summed difference score (SDS: sum total of FDG - MIBI scores) and SDS per segment (%SDS) in each of 5 areas of myocardium (septum, anterior, lateral, inferior area, apex) was calculated and compared between the survival groups (all survival: survival group; survival without ischemic heart disease (IHD): non-IHD survival group) and non-survival group. Both the number of reverse mismatch segments and the %SDS in the septum in the non-IHD survival group were significantly greater than in the non-survival group (3.2+/-1.6 vs 0.5+/-0.6, p<0.05; 0.62+/-0.61 vs -0.11+/-0.19, p<0.05). The receiver-operating characteristics curves for prognosis showed that the area under the curve for the number of reverse mismatch segments in the septum (0.93; confidence interval 0.61-0.98) was significantly greater. CONCLUSION: A reverse mismatch pattern in the septum can predict a good prognosis for patients treated with CRT.

Targeted functional imaging of estrogen receptors with 99mTc-GAP-EDL.

PURPOSE: To evaluate the feasibility of using (99m)Tc-glutamate peptide-estradiol in functional imaging of estrogen receptor-positive [ER(+)] diseases. METHODS: 3-Aminoethyl estradiol (EDL) was conjugated to glutamate peptide (GAP) to yield GAP-EDL. Cellular uptake studies of (99m)Tc-GAP-EDL were conducted in ER(+) cell lines (MCF-7, 13762 and T47D). To demonstrate whether GAP-EDL increases MAP kinase activation, Western blot analysis of GAP-EDL was performed in 13762 cells. Biodistribution was conducted in nine rats with 13762 breast tumors at 0.5-4 h. Each rat was administered (99m)Tc-GAP-EDL. Two animal models (rats and rabbits) were created to ascertain whether tumor uptake of (99m)Tc-GAP-EDL was via an ER-mediated process. In the tumor model, breast tumor-bearing rats were pretreated with diethylstilbestrol (DES) 1 h prior to receiving (99m)Tc-GAP-EDL. In the endometriosis model, part of the rabbit uterine tissue was dissected and grafted to the peritoneal wall. The rabbit was administered with (99m)Tc-GAP-EDL. RESULTS: There was a 10-40% reduction in uptake of (99m)Tc-GAP-EDL in cells treated with DES or tamoxifen compared with untreated cells. Western blot analysis showed an ERK1/2 phosphorylation process with GAP-EDL. Biodistribution studies showed that tumor uptake and tumor-to-muscle count density ratio in (99m)Tc-GAP-EDL groups were significantly higher than those in (99m)Tc-GAP groups at 4 h. Among (99m)Tc-GAP-EDL groups, region of interest analysis of images showed that tumor-to muscle ratios were decreased in blocking groups. In the endometriosis model, the grafted uterine tissue could be visualized by (99m)Tc-GAP-EDL. CONCLUSION: Cellular or tumor uptake of (99m)Tc-GAP-EDL occurs via an ER-mediated process. (99m)Tc-GAP-EDL is a useful agent for imaging functional ER(+) disease.

Correlation between plasma brain natriuretic peptide concentration and lung thallium-201 uptake on exercise thallium perfusion images.

The plasma brain natriuretic peptide (BNP) concentration at rest correlates with left ventricular end-diastolic pressure (LVEDP), left ventricular ejection fraction (LVEF), and pulmonary capillary wedge pressure (PCWP). High lung thallium-201 uptake has been reported to be associated with hemodynamic variables such as LVEDP, LVEF, and PCWP. However, there is no study that has investigated the correlation of plasma BNP concentration with lung thallium-201 uptake. We examined whether the plasma BNP concentration was related to lung thallium-201 uptake. Before exercise, venous blood samples were obtained from 39 patients with old myocardial infarction. We investigated the correlations between plasma BNP concentration and lung thallium-201 uptake, and whether they were related to LVEF, extent of nonviable myocardium, and ischemic myocardium, respectively, with thallium-201 exercise stress testing. The plasma BNP concentration significantly correlated with lung thallium-201 uptake (P < 0.05), nonviable segments (P < 0.01), and LVEF (P < 0.01). Lung thallium-201 uptake correlated with nonviable segments (P < 0.01). Our results suggest that increased secretion of BNP is related to increased lung thallium-201 uptake, and they are related to the extent of nonviable myocardium and decreased left ventricular function. Plasma BNP concentration and lung thalium-201 uptake may reflect the extent of myocardial fibrosis causing myocyte stretch.

Evaluation of myocardial glucose metabolism before and after recovery of myocardial function in patients with tachycardia-induced cardiomyopathy.

BACKGROUND: We assessed left ventricular (LV) function and myocardial glucose metabolism by fluoro-18-deoxyglucose (18F-FDG) positron emission tomography (PET) in patients with tachycardia-induced cardiomyopathy (TC). METHODS: The subjects were 42 patients with heart disease, consisting of 7 patients with TC (61.4 +/- 19.0 years, LVEF 34.1%+/- 10.6%) and 35 with ischemic heart disease (IHD) (63.1 +/- 10.8 years, LVEF 49.9%+/- 13.5%). Five volunteers with normal ECG were the control group. All of the patients underwent 18F-FDG PET and echocardiography, and all of the patients with TC underwent 18F-FDG PET and echocardiography before and 6 months after antitachycardia therapy. Six patients underwent radiofrequency catheter ablation (RFCA) and 1 patient was medically treated with antitachycardia therapy. Myocardial glucose metabolism was assessed semiquantitatively by using the % dose uptake of 60 kg of BW (% dose uptake). RESULTS: Mean % dose uptake of the control group was 5.52 +/- 0.54%. After antitachycardia therapy, LVEF significantly improved (34.1 +/- 10.6% vs 54.3 +/- 13.6%, P < 0.01), and % dose uptake also significantly improved (1.26 +/- 0.55% vs 1.49 +/- 0.62%, P < 0.05). Patients with IHD showed higher % dose uptake than those with TC before antitachycardia therapy (3.18 +/- 1.36 vs 1.26 +/- 0.55%, P < 0.01), controls showed higher value of % dose uptake than TC before antitachycardia therapy (5.52 +/- 0.54% vs 1.26 +/- 0.55%, P < 0.01). CONCLUSION: Semiquantitative analysis of 18F-FDG PET showed that antitachycardia therapy improved myocardial glucose metabolism in patients with TC.