Radionuclide Uptake Research Articles

Pedunculated-type T1 colorectal carcinoma with lung carcinoma metastasis at the deepest invasive portion

We present a rare case of colorectal T1 carcinoma with metastasis of previous lung carcinoma found at the deepest invasive portion. A 61-year-old man presented with cervical lymphadenopathy 18years after undergoing surgery for right lung carcinoma [poorly differentiated adenocarcinoma stage IIb (T3N0M0)]. Contrast-enhanced computed tomography showed enlarged lymph nodes (LNs) in the neck and mediastinal regions. Combined hybrid-F-fluorodeoxyglucose positron emission-computerized tomography showed increased radionuclide uptake in multiple cervical LNs and mediastinal LNs. LN biopsy revealed a poorly differentiated adenocarcinoma, suspected to be a metastatic tumor of the lung. Subsequent colonoscopy revealed a pedunculated-type lesion with a depressed area in the ascending colon. We performed polypectomy as total excisional biopsy; this tumor was composed mainly of moderately differentiated adenocarcinoma, partially mixed with mucinous adenocarcinoma. The pathological findings of the invasive front of the colorectal carcinoma showed poorly differentiated adenocarcinoma with a morphological pattern similar to that of the previous lung carcinoma. Furthermore, immunohistochemical results for the histological type of the deepest invasive portion of the tissue specimen were positive for thyroid transcription factor-1 but negative for Caudal-type homeobox 2. From these morphological and immunohistochemical findings, the final diagnosis was moderately differentiated lung carcinoma, pTX N3 M1b (LN, colon) Stage IV.

Technical Note: Impact of cell repopulation and radionuclide uptake phase on cell survival.

To study theoretically the impact on cell survival of the radionuclide uptake rate inside tumor cells for a single administration of a radiopharmaceutical. The instantaneous-uptake model of O'Donoghue ["The impact of tumor cell proliferation in radioimmunotherapy," Cancer 73, 974-980 (1994)] for a proliferating cell population irradiated by an exponentially decreasing dose-rate is here extended to allow for the monoexponential uptake of the radiopharmaceutical by the targeted cells. The time derivative of the survival curve is studied in detail deducing an expression for the minimum of the surviving fraction and the biologically effective dose (BED). Surviving fractions are calculated over a parameter range that is clinically relevant and broad enough to establish general trends. Specifically, results are presented for the therapy radionuclides Y-90, I-131, and P-32, assuming uptake half-times 1-24 h, extrapolated initial dose-rates 0.5-1 Gy h(-1), and a biological clearance half-life of seven days. Representative radiobiological parameters for radiosensitive and rapidly proliferating tumor cells are used, with cell doubling time equal to 2 days and α-coefficient equal to 0.3 and 0.5 Gy(-1). It is shown that neglecting the uptake phase of the radiopharmaceutical (i.e., assuming instantaneous-uptake) results in a sizeable over-estimation of cell-kill (i.e., under-estimation of cell survival) even for uptake half-times of only a few hours. The differences between the exponential-uptake model and the instantaneous-uptake model become larger for high peak dose-rates, slow uptakes, and (slightly) for long-lived radionuclides. Moreover, the sensitivity of the survival curve on the uptake model was found to be higher for the tumor cells with the larger α-coefficient. The exponential-uptake rate of the radiopharmaceutical inside targeted cells appears to have a considerable effect on the survival of a proliferating cell population and might need to be considered in radiobiological models of tumor cell-kill in radionuclide therapy.

Comparison of the radiotoxicity of the 99mTc-labeled compounds 99mTc-pertechnetate, 99mTc-HMPAO and 99mTc-MIBI

Purpose: In addition to gamma radiation, 99mTc emits low-energy Auger electrons with path-lengths of nanometers to micrometers that cannot be utilized for diagnostic procedures; however, they have frequently been discussed for therapeutic applications. We compared radiotoxicity of three 99mTc-labeled radiopharmaceuticals with differences in the subcellular distribution.Materials and methods: The intracellular radionuclide uptake and subcellular distribution of [99mTc]-pertechnetate (99mTc-pertechnetate), [99mTc]Tc-hexamethyl-propylene-aminoxime (99mTc-HMPAO) and [99mTc]Tc-hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) were quantified in rat thyroid FRTL-5 cells. Radiotoxicity was compared using late phosphorylated histone H2AX (γH2AX) foci as a marker for unrepaired DNA double-strand breaks (DNA-DSB) and clonogenic cell survival.Results: 99mTc-HMPAO showed a substantially higher uptake into the nucleus and the membrane/organelles than 99mTc-pertechnetate or 99mTc-MIBI. The colony-forming assay showed that 99mTc-pertechnetate and 99mTc-HMPAO caused a similar reduction in cell survival. 99mTc-MIBI is less radiotoxic in terms of the estimated nucleus dose and induced the fewest number of γH2AX foci compared with the other 99mTc-tracers, and 99mTc-HMPAO induced a fewer number of γH2AX foci than 99mTc-pertechnetate.Conclusions: Our findings reveal that clonogenic cellular survival is not solely determined by the DNA-DSB response. This finding may suggest the involvement of extra-nuclear radiosensitive targets in cell inactivation. For example, the mitochondria or the cell membrane could be affected by 99mTc-HMPAO.

Somatostatin receptor-targeted radionuclide therapy for progressive meningioma: benefit linked to 68Ga-DOTATATE/-TOC uptake.

The prognosis of patients with progressive meningioma after failure of surgery and radiotherapy is poor. We retrospectively evaluated the safety and efficacy of somatostatin-receptor (SSTR)-targeted radionuclide therapy (177Lu-DOTATATE [n = 16], 90Y-DOTATOC [n = 3], or both [n = 1]) in patients with progressive, treatment-refractory meningiomas (5 World Health Organization [WHO] grade I, 7 WHO grade II, 8 WHO grade III) and in part multifocal disease (17 of 20 patients). SSTR radionuclide treatment (median of 3 treatment cycles, median administered dose/cycle 7400 MBq) led to a disease stabilization in 10 of 20 patients for a median time of 17 months. Stratification according to WHO grade showed a median progression-free survival (PFS) of 32.2 months for grade I tumors, 7.2 for grade II, and 2.1 for grade III. PFS at 6 months was 100% for grade I, 57% for grade II, and 0% for grade III. Median overall survival was 17.2 months in WHO grade III patients and not reached for WHO I and II at a median follow-up of 20 months. In the analysis of single meningioma lesions, maximal and mean standardized uptake values in pretherapeutic 68Ga-DOTATOC/-TATE PET/CT were significantly higher in those lesions with radiographic stability after 6 months. In line with this, high expression of SSTR via immunohistochemistry was associated with PFS >6 months. SSTR-targeted radionuclide treatment has activity in a subset of patients with meningioma. Expression of SSTR via immunohistochemistry or radionuclide uptake might serve as a predictive biomarker for outcome to facilitate individualized treatment optimization in patients with uni- and multifocal meningiomas.

Percutaneous microwave ablation of thyroid nodules: efficacy evaluation with 99m Tc - pertechnetate and 99mTc-MIBI functional imaging

Background : Local ablave treatments play an important role for paents who cannot be treated surgically. Radiofrequency ablaon is a well-established alternave to surgical treatment of thyroid nodules, however it also has disadvantages. Microwave ablaon (MWA) is a new minimally invasive treatment promising several improvements. The aim of this retrospecve study was to evaluate the effects of microwave ablaon on thyroid nodules by 99m Tc-pertechnetate and 99m Tc-MIBI scingraphy. Materials and Methods : 30 paents with overall 40 nodules were treated. For the ablaon of thyroid nodules, a microwave generator working with frequencies from 902 to 928 MHz was used. The ablaonme ranged between 120 and 300 seconds per ablaon zone. The target temperatures ranged between 60-80 °C. Pre- and post- intervenonal, the radionuclide uptake was determined using a thyroid specific scinllaon camera. For 27 cold nodules 99m Tc-MIBI was used for evaluaon; 13 indifferent nodules were measured with 99m Tc-pertechnetate. Results: The relave change of uptake was detected as a quoent of pre- and post- therapeuc uptake. The stascal analysis of scingraphy data proved the e fficacy of microwave ablaon. 99m Tc-pertechnetate scingraphy showed an uptake reducon of 39% (range 9 to 85%). 99m Tc-MIBI imaging showed a median reducon of 40% (p<0.01) (range 7 to 100%). Conclusion: The determined results show the effecveness of MWA as a treatment opon for benign thyroid nodules. With funconal scingraphy a significant acvity decrease could be detected in the ablaon zone; hence a verificaon of affecvity was p ossible a=er a short period ofme.

Natural radionuclide uptake by mosses in eastern Serbia in 2008-2013.

The results of the study on natural radionuclide content in 102 samples of the moss species randomly collected in 2008- 2013 at 30 locations of eastern Serbia are presented in the paper. The activity concentration values of 238U, 226Ra, 232Th, 40K, and 7Be determined by gamma spectrometry were within the intervals: 238U (1.1-50) Bq kg(-1), 226Ra (1.1-41) Bq kg(-1), 232Th (1.4-28) Bq kg(-1), 40K (64-484) Bq kg(-1) and 7Be (88-227) Bq kg(-1), not standing out of the average data reported for this region. The distribution of the obtained data for 226Ra, 232Th, and 238U activity concentration in the analysed mosses has shown values up to 10 Bq kg(-1) with frequencies 47.1 %, 54.9 % and 48.0 %, respectively. The obtained activity concentration values of primordial 40K and cosmogenic radionuclide 7Be were up to 500 Bq kg(-1) and about 90 % of all the results for 7Be uptake by mosses were in the 200-250 Bq kg(-1) concentration range.

Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule 68Ga-ABY-025 in Breast Cancer Patients.

(68)Ga-ABY-025 is a radiolabeled Affibody molecule for in vivo diagnosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer tumors with PET. The aim of the present work was to measure the biodistribution and estimate the radiation dosimetry of (68)Ga-ABY-025 for 2 different peptide mass doses in a single group of patients using dynamic and serial whole-body PET/CT. Eight patients with metastatic breast cancer were included. Each patient underwent an abdominal 45-min dynamic and 3 whole-body PET/CT scans at 1, 2, and 4 h after injection of a low peptide dose (LD) and a high peptide dose (HD), with approximately the same amount of radioactivity, in separate investigations 1 wk apart. As input to the absorbed dose calculations, volumes of interest were drawn on all clearly identifiable source organs: liver, kidneys, spleen, descending aorta, and upper large intestine. Absorbed doses were calculated using OLINDA/EXM, version 1.1. Of the major organs, the highest radionuclide uptake at 1, 2, and 4 h after injection was observed in the kidneys and liver. The highest absorbed organ doses were seen in the kidneys, followed by the liver for both LD and HD (68)Ga-ABY-025. Absorbed doses to liver and kidneys were slightly but significantly higher for LD. Total effective dose was 0.030 ± 0.003 mSv/MBq for LD and 0.028 ± 0.002 mSv/MBq for HD. The effective dose for a typical 200-MBq administration of (68)Ga-ABY-025 is 6.0 mSv for LD and 5.6 mSv for HD. Therefore, from a radiation dosimetry point of view, HD is preferred for PET/CT evaluation of HER2-expressing breast cancer tumors. These effective doses are somewhat higher than earlier published values for other (68)Ga-labeled tracers, such as 0.021 ± 0.003 mSv/MBq for (68)Ga-DOTATATE and (68)Ga-DOTATOC, mainly because of higher uptake in liver and kidney.

Prediction of traumatic avascular necrosis of the femoral head by single photon emission computerized tomography and computerized tomography: an experimental study in dogs

ObjectiveTo evaluate the femoral head perfusion and to predict the traumatic avascular necrosis (AVN) of the femoral head by single photon emission computerized tomography and computerized tomography (SPECT/CT). MethodsTotally 18 adult beagle dogs were divided randomly into three equal-sized (n=6) groups. Subsequently different degrees of ischemia model were developed by destroying blood vessels of the femoral head. The left hip received sham operation as normal control and the right hip underwent blood interruption. In Group A, the ligamentum teres was cut off. In Group B, the marrow cavity of the right femoral neck was destroyed while in Group C, the soft tissues at the base of the femoral neck were stripped in addition to the resection of the ligamentum teres and destruction of the marrow cavity. Three hours after surgery, SPECT/ CT was performed. Laser Doppler Flowmetry (LDF) measurements were also obtained at three different time points (before operation, immediately and three hours after operation) in order to assess the change process of blood supply to the femoral head. ResultsSPECT/CT showed no significant difference in the radionuclide uptake between the right and left femoral heads in Group A (/=-0.09, P=0.94) and Group B (t= 0.52, P=0.62). However, in Group C, it was 261±62 for the right femoral head, only 12% of that in the left femoral head. LDF measurements indicated that the femoral head perfusion was decreased from (45.0±3.3) PU to (39.1±3.7) PU in Group A, from (44.0±2.7) PU to (34.3±2.6) PU in Group B, and from (47.3 ±2.1) PU to (4.96±0.6) PU in Group C immediately after operation. However, the perfusion was restored and returned to normal values three hours after operation except in Group C. ConclusionSPECT/CT could assess the perfusion of the femoral head semiquantitatively, which might be useful in predicting the development of traumatic AVN.

Inter-comparison of dynamic models for radionuclide transfer to marine biota in a Fukushima accident scenario

We report an inter-comparison of eight models designed to predict the radiological exposure of radionuclides in marine biota. The models were required to simulate dynamically the uptake and turnover of radionuclides by marine organisms.Model predictions of radionuclide uptake and turnover using kinetic calculations based on biological half-life (TB1/2) and/or more complex metabolic modelling approaches were used to predict activity concentrations and, consequently, dose rates of 90Sr, 131I and 137Cs to fish, crustaceans, macroalgae and molluscs under circumstances where the water concentrations are changing with time. For comparison, the ERICA Tool, a model commonly used in environmental assessment, and which uses equilibrium concentration ratios, was also used. As input to the models we used hydrodynamic forecasts of water and sediment activity concentrations using a simulated scenario reflecting the Fukushima accident releases.Although model variability is important, the intercomparison gives logical results, in that the dynamic models predict consistently a pattern of delayed rise of activity concentration in biota and slow decline instead of the instantaneous equilibrium with the activity concentration in seawater predicted by the ERICA Tool. The differences between ERICA and the dynamic models increase the shorter the TB1/2 becomes; however, there is significant variability between models, underpinned by parameter and methodological differences between them.The need to validate the dynamic models used in this intercomparison has been highlighted, particularly in regards to optimisation of the model biokinetic parameters.

The value of SPECT/CT in carpal boss.

To assess the value of SPECT/CT in patients with carpal boss (CB). In 24 wrists with CB (18 right-sided, 6 left-sided) in 21 patients, planar images and SPECT/CT images were obtained. Three patients had bilateral CB. The grade of uptake (0 absent, 1 low, 2 moderate, 3 high) on planar imaging and SPECT/CT was assessed and compared with CT findings, clinical symptoms and follow-up findings. CB affected carpometacarpal joint II in 4 wrists, carpometacarpal joint III in 17 wrists and both carpometacarpal joints II and III in 3 wrists. Of the 24 CB, 12 (50 %) were active (i.e. increased radionuclide uptake) on planar images and 18 (75 %) on SPECT/CT images. Of the 17 symptomatic CB, 10 (59 %) were active on planar images and 14 (82 %) were active (mean grade 1.9, range 1 - 3) on SPECT/CT images. Of the 7 asymptomatic CB, 2 were active on planar images and 4 were active (mean grade 1.25, range 1 - 2) on SPECT/CT images. CT alone showed CB in all patients and an accessory ossicle (os styloideum) in 8 wrists. MR imaging was available in 7 patients and positive for CB in 5 (sensitivity 71 %). Plain radiographs were available in 17 patients and positive in 10 (59 %). Therapeutic infiltration of the CB was performed in 9 patients, and resection of the CB in 7 patients. SPECT/CT provides important morphological and metabolic information for the clinical assessment of CB, but because SPECT/CT tends to overestimate the clinical importance of CB, we recommend that planar images should still be obtained.

Biological effects of α-radiation exposure by 241Am in Arabidopsis thaliana seedlings are determined both by dose rate and 241Am distribution

Human activity has led to an increasing amount of radionuclides in the environment and subsequently to an increased risk of exposure of the biosphere to ionising radiation. Due to their high linear energy transfer, α-emitters form a threat to biota when absorbed or integrated in living tissue. Among these, 241Am is of major concern due to high affinity for organic matter and high specific activity. This study examines the dose-dependent biological effects of α-radiation delivered by 241Am at the morphological, physiological and molecular level in 14-day old seedlings of Arabidopsis thaliana after hydroponic exposure for 4 or 7 days. Our results show that 241Am has high transfer to the roots but low translocation to the shoots. In the roots, we observed a transcriptional response of reactive oxygen species scavenging and DNA repair pathways. At the physiological and morphological level this resulted in a response which evolved from redox balance control and stable biomass at low dose rates to growth reduction, reduced transfer and redox balance decline at higher dose rates. This situation was also reflected in the shoots where, despite the absence of a transcriptional response, the control of photosynthesis performance and redox balance declined with increasing dose rate. The data further suggest that the effects in both organs were initiated in the roots, where the highest dose rates occurred, ultimately affecting photosynthesis performance and carbon assimilation. Though further detailed study of nutrient balance and 241Am localisation is necessary, it is clear that radionuclide uptake and distribution is a major parameter in the global exposure effects on plant performance and health.

Bright Lu2O3:Eu Thin‐Film Scintillators for High‐Resolution Radioluminescence Microscopy

The performance of a new thin-film Lu2 O3 :Eu scintillator for single-cell radionuclide imaging is investigated. Imaging the metabolic properties of heterogeneous cell populations in real time is an important challenge with clinical implications. An innovative technique called radioluminescence microscopy has been developed to quantitatively and sensitively measure radionuclide uptake in single cells. The most important component of this technique is the scintillator, which converts the energy released during radioactive decay into luminescent signals. The sensitivity and spatial resolution of the imaging system depend critically on the characteristics of the scintillator, that is, the material used and its geometrical configuration. Scintillators fabricated using conventional methods are relatively thick and therefore do not provide optimal spatial resolution. A thin-film Lu2 O3 :Eu scintillator is compared to a conventional 500 μm thick CdWO4 scintillator for radioluminescence imaging. Despite its thinness, the unique scintillation properties of the Lu2 O3 :Eu scintillator allow us to capture single-positron decays with fourfold higher sensitivity, which is a significant achievement. The thin-film Lu2 O3 :Eu scintillators also yield radioluminescence images where individual cells appear smaller and better resolved on average than with the CdWO4 scintillators. Coupled with the thin-film scintillator technology, radioluminescence microscopy can yield valuable and clinically relevant data on the metabolism of single cells.

Computed tomography and scintigraphy for evaluation of dental disease in the horse

SummaryComputed tomography (CT) uses x‐ray beams and reconstructive computer technology to create tomographic slices (sections) of the area being imaged. Computed tomography has higher contrast resolution than conventional radiography allowing for more accurate differentiation of soft tissues and fluids. This form of 3D imaging removes problems caused by superimposition of multiple anatomical structures, which is a major impediment when viewing radiographs of the equine head. Once the images are acquired, multi‐planar and 3D reconstructions can be performed to view different teeth or associated structures in an optimal way. Anatomical and pathological changes in the dental tissues, periodontal tissues, alveolar bone and adjacent sinuses can then be assessed. Scintigraphy with 99m technetium methyl‐diphosphate (methylene‐diphosphonate) can detect changes in bone that precede radiographic changes, and this makes it a very useful imaging modality for diagnosis of early periapical infection of the equine cheek teeth. Additionally, it is invaluable for imaging suspected infections of supernumerary or dysplastic teeth where the results of radiography or even CT may be equivocal. Periapical infections of the cheek teeth typically result in focal and intense increased radionuclide uptake located over the apical region of the affected tooth.

Benign Lymphoepithelial Lesion of Parotid Gland and Secondary Amyloidosis as Concurrent Manifestations in Sjögren's Syndrome.

Benign Lymphoepithelial Lesion of Parotid Gland and Secondary Amyloidosis as Concurrent Manifestations in Sjögren's Syndrome.

Oncological whole-body staging in integrated 18F-FDG PET/MR: Value of different MR sequences for simultaneous PET and MR reading

ObjectiveTo evaluate different magnetic resonance (MR) imaging sequences in integrated positron emission tomography (PET)/MR concerning their ability to detect tumors and allocate increased radionuclide uptake on 18F-fluorodeoxyglucose (18F-FDG) PET in intraindividual comparison with computed tomography (CT) from PET/CT. Material and methodsSixty-one patients (34 female, 27 male, mean age 57.6y) who were examined with contrast-enhanced PET/CT and subsequent PET/MR (mean delay for PET/MR after injection: 147±43min) were included. A maximum of ten 18F-FDG-avid lesions per patient were analyzed on CT from PET/CT and with the following MR sequences from PET/MR: T2, turbo inversion recovery magnitude (TIRM), non-enhanced T1, contrast-enhanced T1, and diffusion-weighted imaging (DWI). All lesions were rated using a four-point ordinal scale (scored from 0 to 3) concerning visual detectability of the lesion against the surrounding background and anatomical allocation of the PET finding. In each category (detectability and allocation), Wilcoxon rank sum tests were performed. Bonferroni–Holm correction was performed to prevent α-error accumulation. ResultsIn 225 18F-FDG-avid lesions (156 confirmed as malignant by radiological follow up, 69 by histopathology), visual detectability was comparably high on CT (mean: 2.5±0.9), TIRM (mean: 2.5±0.9), T2 (mean: 2.4±0.9), and DWI (mean: 2.5±1.0) and was significantly higher than on non-enhanced T1 (mean: 2.2±1.0). While anatomic allocation of the PET finding was comparable with CT (mean: 2.6±0.7), T2 (mean: 2.6±0.7), and TIRM (mean: 2.8±0.7), it was significantly higher compared to DWI (mean: 2.1±1.0) and non-enhanced T1 (mean: 2.4±0.8). ConclusionIn conclusion, T2, TIRM, and contrast-enhanced T1 provide a high quality of lesion detectability and anatomical allocation of FDG-avid foci. Their performance is at least comparable to contrast-enhanced PET/CT. Non-enhanced T1 may be omitted and the necessity of DWI should be further investigated for specific questions, such as assessment of the liver.

MP87-11 ALKALINE PHOSPHATASE VELOCITY AS A PREDICTOR OF BONE METASTASIS AND OVERALL SURVIVAL IN CASTRATE RESISTANT PROSTATE CANCER PATIENTS

from aggressive treatment. Ryan et al reported bone scan flare in 11 of 23 (48%) evaluable patients treated with abiraterone plus prednisone for metastatic and chemotherapy naive CRPC patients. To our knowledge this is the first report about ALP flare following enzalutamide treatment. METHODS: 40 patients with CRPC were treated with enzalutamide 160 mg, 20 patients were chemotherapy naive and 20 patients were chemotherapy (Docetaxel) resistant. RESULTS: 2 of 40(5%) patients experienced ALP flare. ALP began to increase 2 weeks after initiation of enzalutamide, peaked at 4 weeks and began to decrease afterwards. PSA decreased in both cases and 90% decrease was observed. In both patients, bone pain completely alleviated and the patients became analgesic drugs free. In one case. PSA value decreased from 957 to 111 ng/ml and ALP value increased 382 IU/l to 1442 in 4 weeks then decreased to 400 after 16 weeks. Bone scan flare was also found. The patient does well maintaining good ADL. CONCLUSIONS: A flare phenomenon, defined by an increase in skeletal radionuclide uptake, shortly after initiating hormonal therapy or chemotherapy was first described in the mid 1970s in patients with breast carcinoma metastatic to the skeleton using 87mstrontium and later 99mtechnetium bone scintigrams. This flare phenomenon has also been described in patients with prostate carcinoma metastatic to the skeleton 2 weeks after castration, with a return to baseline levels 2 months later. However, the reported frequency of a flare is variable, depending on timing of posttreatment scintigram. The simplicity, ready availability and cost-effectiveness of serum alkaline phosphatase activity as a prognostic index render it attractive to the clinician, particularly early in the course of prostatic carcinoma. Measuring the flare in alkaline phosphatase activity within 1 month of orchiectomy may permit early identification of patients in whom the disease is likely to progress rapidly and who would potentially benefit from aggressive treatment.

MP87-10 ALP AND BONE SCAN FLARE FOLLOWING ENZALUTAMIDE TREATMENT OF CASTRATION RESISTANT PROSTATE CANCER (CRPC) WITH BONE METASTASIS

You have accessJournal of UrologyProstate Cancer: Advanced III1 Apr 2015MP87-10 ALP AND BONE SCAN FLARE FOLLOWING ENZALUTAMIDE TREATMENT OF CASTRATION RESISTANT PROSTATE CANCER (CRPC) WITH BONE METASTASIS Senji Hoshi, Kunihisa Nezu, Hidenori Kanno, Teppei Ookubo, Mituharu Sasaki, Kenji Numahata, Kiyotugu Hoshi, Satoru Kanto, Isoji Sasagawa, Yuuichi Ishizuka, Hideaki Izumi, Kunio Ono, and Vladimir Bilim Senji HoshiSenji Hoshi More articles by this author , Kunihisa NezuKunihisa Nezu More articles by this author , Hidenori KannoHidenori Kanno More articles by this author , Teppei OokuboTeppei Ookubo More articles by this author , Mituharu SasakiMituharu Sasaki More articles by this author , Kenji NumahataKenji Numahata More articles by this author , Kiyotugu HoshiKiyotugu Hoshi More articles by this author , Satoru KantoSatoru Kanto More articles by this author , Isoji SasagawaIsoji Sasagawa More articles by this author , Yuuichi IshizukaYuuichi Ishizuka More articles by this author , Hideaki IzumiHideaki Izumi More articles by this author , Kunio OnoKunio Ono More articles by this author , and Vladimir BilimVladimir Bilim More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1955AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES An increase in alkaline phosphatase (ALP) activity has been described in patients with metastatic prostatic carcinoma within weeks of medical or surgical castration, and is believed to be of positive prognostic value for the success of systemic therapy. Measuring the flare in ALP activity within 1 month of orchiectomy may facilitate early identification of patients in whom the disease is likely to progress rapidly and who would potentially benefit from aggressive treatment. Ryan et al reported bone scan flare in 11 of 23 (48%) evaluable patients treated with abiraterone plus prednisone for metastatic and chemotherapy naive CRPC patients. To our knowledge this is the first report about ALP flare following enzalutamide treatment. METHODS 40 patients with CRPC were treated with enzalutamide 160 mg, 20 patients were chemotherapy naive and 20 patients were chemotherapy (Docetaxel) resistant. RESULTS 2 of 40(5%) patients experienced ALP flare. ALP began to increase 2 weeks after initiation of enzalutamide, peaked at 4 weeks and began to decrease afterwards. PSA decreased in both cases and 90% decrease was observed. In both patients, bone pain completely alleviated and the patients became analgesic drugs free. In one case. PSA value decreased from 957 to 111 ng/ml and ALP value increased 382 IU/l to 1442 in 4 weeks then decreased to 400 after 16 weeks. Bone scan flare was also found. The patient does well maintaining good ADL. CONCLUSIONS A flare phenomenon, defined by an increase in skeletal radionuclide uptake, shortly after initiating hormonal therapy or chemotherapy was first described in the mid 1970s in patients with breast carcinoma metastatic to the skeleton using 87mstrontium and later 99mtechnetium bone scintigrams. This flare phenomenon has also been described in patients with prostate carcinoma metastatic to the skeleton 2 weeks after castration, with a return to baseline levels 2 months later. However, the reported frequency of a flare is variable, depending on timing of posttreatment scintigram. The simplicity, ready availability and cost-effectiveness of serum alkaline phosphatase activity as a prognostic index render it attractive to the clinician, particularly early in the course of prostatic carcinoma. Measuring the flare in alkaline phosphatase activity within 1 month of orchiectomy may permit early identification of patients in whom the disease is likely to progress rapidly and who would potentially benefit from aggressive treatment. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e1087-e1088 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Senji Hoshi More articles by this author Kunihisa Nezu More articles by this author Hidenori Kanno More articles by this author Teppei Ookubo More articles by this author Mituharu Sasaki More articles by this author Kenji Numahata More articles by this author Kiyotugu Hoshi More articles by this author Satoru Kanto More articles by this author Isoji Sasagawa More articles by this author Yuuichi Ishizuka More articles by this author Hideaki Izumi More articles by this author Kunio Ono More articles by this author Vladimir Bilim More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Dynamic modelling of radionuclide uptake by marine biota: application to the Fukushima nuclear power plant accident

The dynamic model D-DAT was developed to study the dynamics of radionuclide uptake and turnover in biota and sediments in the immediate aftermath of the Fukushima accident. This dynamics is determined by the interplay between the residence time of radionuclides in seawater/sediments and the biological half-lives of elimination by the biota. The model calculates time-variable activity concentration of 131I, 134Cs, 137Cs and 90Sr in seabed sediment, fish, crustaceans, molluscs and macroalgae from surrounding activity concentrations in seawater, with which to derive internal and external dose rates.A central element of the model is the inclusion of dynamic transfer of radionuclides to/from sediments by factorising the depletion of radionuclides adsorbed onto suspended particulates, molecular diffusion, pore water mixing and bioturbation, represented by a simple set of differential equations coupled with the biological uptake/turnover processes. In this way, the model is capable of reproducing activity concentration in sediment more realistically.The model was used to assess the radiological impact of the Fukushima accident on marine biota in the acute phase of the accident. Sediment and biota activity concentrations are within the wide range of actual monitoring data. Activity concentrations in marine biota are thus shown to be better calculated by a dynamic model than with the simpler equilibrium approach based on concentration factors, which tends to overestimate for the acute accident period. Modelled dose rates from external exposure from sediment are also significantly below equilibrium predictions. The model calculations confirm previous studies showing that radioactivity levels in marine biota have been generally below the levels necessary to cause a measurable effect on populations. The model was used in mass-balance mode to calculate total integrated releases of 103, 30 and 3 PBq for 131I, 137Cs and 90Sr, reasonably in line with previous estimates.

Predictive value of single photon emission computerized tomography and computerized tomography in osteonecrosis after femoral neck fracture: a prospective study.

Osteonecrosis of the femoral head (ONFH) is a very common complication after femoral neck fracture. The purpose of this study was to assess the femoral head vascularity after femoral neck fracture using single photon emission computerized tomography and computerized tomography (SPECT/CT), and to evaluate its value in predicting ONFH. Between January 2008 and March 2011, 120 patients diagnosed with femoral neck fracture underwent SPECT-CT before the internal fixation. The fracture was classified according to the Garden classification. The ratios of the radionuclide uptake of the fractured femoral head to that of the contralateral femoral head (F/N) were calculated to assess the femoral head vascularity. After a minimum of two years' follow-up, magnetic resonance imaging (MRI) was used as the "gold standard" for the diagnosis of possible ONFH. A total of 114 patients completed the study. The SPECT/CT examination showed that the F/N ratios of Garden I, II, III and IV were 2.6, 1.8, 0.8, and 0.6, respectively. At the time of the most recent follow-up, osteonecrosis developed in two of the 27 patients who had a Garden Stage-II fracture, in eight of the 34 patients who had a Garden Stage-III fracture, and nine of the 27 patients who had a Garden Stage-VI fracture. With a cutoff of 0.55 from the receiver operating characteristic (ROC) curve, F/N ratio showed a sensitivity of 97%, a specificity of 79%, a positive predictive value of 95%, and a negative predictive value of 19%. SPECT-CT proved to be reliable and valid for predicting ONFH after femoral neck fracture.

Quantification of radionuclide uptake levels for primary bone tumors

The purpose of the study is to quantify the level of uptake of administered radionuclide in primary bone tumors for patients undergoing bone scintigraphy. Retrospective study on 48 patient's scintigrams to quantify the uptake levels of administered radiopharmaceuticals was performed in a nuclear medicine unit in Ghana. Patients were administered with activity ranging between 0.555 and 1.110 MBq (15–30 mCi), and scanned on Siemens e.cam SPECT system. Analyses on scintigrams were performed with Image J software by drawing regions of interest (ROIs) over identified hot spots (pathologic sites). Nine skeletal parts namely cranium, neck, shoulder, sacrum, sternum, vertebra, femur, ribcage, and knee were considered in the study, which involved 96 identified primary tumors. Radionuclide uptakes were quantified in terms of the estimated counts of activity per patient for identified tumor sites. Average normalized counts of activity (nGMC) per patient ranged from 5.2759 ± 0.6590 cts/mm2/MBq in the case of cranium tumors to 72.7569 ± 17.8786 cts/mm2/MBq in the case of ribcage tumors. The differences in uptake levels could be attributed to different mechanisms of Tc-99m MDP uptake in different types of bones, which is directly related to blood flow and degree of osteoblastic activity. The overall normalized count of activity for the 96 identified tumors was estimated to be 23.0350 ± 19.5424 cts/mm2/MBq. The study revealed highest uptake of activity in ribcage and least uptake in cranium. Quantification of radionuclide uptakes in tumors is important and recommended in assessing patient's response to therapy, doses to critical organs and in diagnosing tumors.