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Purpose Genomic profiling of biopsied tissue is the basis for precision cancer therapy. However, biopsied materials may not contain sufficient amounts of tumor deoxyribonucleonic acid needed for the analysis. We propose a method to determine the adequacy of specimens for performing genomic profiling by quantifying their metabolic activity. Methods We estimated the average density of tumor cells in biopsy specimens needed to successfully perform genomic analysis following the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) protocol from the minimum amount of deoxyribonucleonic acid needed and the volume of tissue typically used for analysis. The average 18 F-FDG uptake per cell was assessed by incubating HT-29 adenocarcinoma tumor cells in 18 F-FDG containing solution and then measuring their activity with a scintillation well counter. Consequently, we evaluated the response of two devices around the minimum expected activities which would indicate genomic profiling adequacy of biopsy specimens obtained under 18 F-FDG PET/CT guidance. Surrogate samples obtained using 18G core needle biopsies of gels containing either 18 F-FDG-loaded cells in the expected concentrations or the corresponding activity were measured using autoradiography and a scintillation well counter. Autoradiography was performed using a CCD-based device with real-time image display as well as with digital autoradiography imaging plates following a 30-min off-line protocol for specimen activity determination against previously established calibration. Results Cell incubation experiments and estimates obtained from quantitative autoradiography of biopsy specimens (QABS) indicate that specimens acquired under 18 F-FDG PET/CT guidance that contained the minimum amount of cells needed for genomic profiling would have an average activity concentration in the range of about 3 to about 9 kBq/mL. When exposed to specimens with similar activity concentration, both a CCD-based autoradiography device and a scintillation well counter produced signals with sufficient signal-to-background ratio for specimen genomic adequacy identification in less than 10 min, which is short enough to allow procedure guidance. Conclusion Scintillation well counter measurements and CCD-based autoradiography have adequate sensitivity to detect the tumor burden needed for genomic profiling during 18 F-FDG PET/CT-guided 18G core needle biopsies of liver adenocarcinoma metastases.

Introduction Quantitative small animal radionuclide imaging studies are often carried out with the intention of estimating the total radioactivity content of various tissues such as the radioactivity content of mouse xenograft tumors exposed to putative diagnostic or therapeutic agents. We show that for at least one specific application, positron projection imaging (PPI) and PET yield comparable estimates of absolute total tumor activity and that both of these estimates are highly correlated with direct well-counting of these same tumors. These findings further suggest that in this particular application, PPI is a far more efficient data acquisition and processing methodology than PET. Methods Forty-one athymic mice were implanted with PC3 human prostate cancer cells transfected with prostate-specific membrane antigen (PSMA (+)) and one additional animal (for a total of 42) with a control blank vector (PSMA (−)). All animals were injected with [ 18 F] DCFPyl, a ligand for PSMA, and imaged for total tumor radioactivity with PET and PPI. The tumors were then removed, assayed by well counting for total radioactivity and the values between these methods intercompared. Results PET, PPI and well-counter estimates of total tumor radioactivity were highly correlated (R 2 > 0.98) with regression line slopes near unity (0.95 Conclusion Total mouse xenograft tumor radioactivity can be measured with PET or PPI with an accuracy comparable to well counting if certain experimental and pharmacokinetic conditions are met. In this particular application, PPI is significantly more efficient than PET in making these measurements.

Introduction We describe a simple fixture that can be added to the imaging bed of a small-animal PET scanner that allows for automated counting of multiple organ or tissue samples from mouse-sized animals and counting of injection syringes prior to administration of the radiotracer. The combination of imaging and counting capabilities in the same machine offers advantages in certain experimental settings. Methods A polyethylene block of plastic, sculpted to mate with the animal imaging bed of a small-animal PET scanner, is machined to receive twelve 5-ml containers, each capable of holding an entire organ from a mouse-sized animal. In addition, a triangular cross-section slot is machined down the centerline of the block to secure injection syringes from 1-ml to 3-ml in size. The sample holder is scanned in PET whole-body mode to image all samples or in one bed position to image a filled injection syringe. Total radioactivity in each sample or syringe is determined from the reconstructed images of these objects using volume re-projection of the coronal images and a single region-of-interest for each. We tested the accuracy of this method by comparing PET estimates of sample and syringe activity with well counter and dose calibrator estimates of these same activities. Results PET and well counting of the same samples gave near identical results (in MBq, R 2 =0.99, slope=0.99, intercept=0.00-MBq). PET syringe and dose calibrator measurements of syringe activity in MBq were also similar ( R 2 =0.99, slope=0.99, intercept=− 0.22-MBq). Conclusion A small-animal PET scanner can be easily converted into a multi-sample and syringe counting device by the addition of a sample block constructed for that purpose. This capability, combined with live animal imaging, can improve efficiency and flexibility in certain experimental settings.

AIM: To correlate between the radionuclide in vitro plasma sampling method (using single and dual blood samples) and Gates’ GFR measurement using Tc-99m diethylene triamine penta-acetic acid (Tc-99m DTPA) renal scintigraphy (in vivo method). METHODS: This study included 40 renal donors (group 1) and 40 patients with obstructive uropathy (group 2). Group 1 included 22 males and 18 females with an age range from 22 to 65 years, while group 2 included 24 males and 16 females with age range 27 to 64 years. Both groups subjected to renal Scintigraphy after administration of 5 mCi 99m-Tc DTPA, GFR was calculated using Gates’ method (in vivo method), then plasma sampling was acquired at 60 mins and 180 mins post-injection of the tracer, samples were counted in well counter and GFR was calculated using in vitro technique either using single plasma sample (SPSM 60 mins) or dual sample (DPSM 60 & 180 min). Additionally, GFR was measured by estimated equations based on serum creatinine. RESULTS: In group 1, the mean GFR using in vivo Gates’ method was 115.7 ± 29 ml/min, while using the SPSM was 100.1 ± 16.1 ml/min, and the DPSM was 100.3 ± 20.1 ml/min. In group 2, mean GFR using in vivo method was 74.1 ± 14.5 ml/min, while using in vitro SPSM it was 77.5 ± 24.9 ml/min and DPSM was 76.8 ± 24.8 ml/min. There was no significant difference between mean GFR values using in vivo and in vitro methods (single or dual samples) in group 1 and 2 (p > 0.05). There is high significant correlation between SPSM and DPSM in groups 1 and 2 (r = 0.90, r = 0.91 respectively), moderate significant correlation was found between in vivo Gates’ method and in vitro SPSM in group 1 and 2 (r = 0.46 and 0.57 respectively) and moderate correlation was evident between in vivo and in vitro DPSM in both groups (r = 0.42 and 0.68 respectively). By using the DPSM as the reference standard significant high correlation was found with SPSM and significant-high moderate correlation with in vivo Gates’ scintigraphic method. Conclusion: In vitro plasma sampling considered as a reliable, accurate |method for GFR calculation yet it considered relatively complex, both single and dual sample in vitro techniques showed a very high correlation, and hence SPSM can replace DPSM. CONCLUSION: Renal scintigraphy and GFR estimation using Gates’ in vivo method is considered inaccurate, yet given its simplicity in performance it can still be used if corrected GFR is standardised for Egyptian population-based on studies with large numbers of patients from multiple centres.

Background: In order to obtain a reliable 177Lu-DOTATATE therapy dosimetry, it is crucial to acquire accurate and precise activity measurements with the radionuclide calibrator, the SPECT/CT camera, and the NaI(Tl) well counter. The aim of this study was to determine, in a clinical context, the accuracy and the precision of their activity quantification over a range of activities and time. Ninety-three 177Lu sources from the manufacturer were measured in the radionuclide calibrator over 2.5 years to evaluate its calibration accuracy and precision compared to the manufacturer’s value. A NEMA 2012/IEC 2008 phantom was filled with a 177Lu activity concentration sphere-to-background ratio of five. It was acquired with the SPECT/CT camera to determine the reconstruction parameters offering the best compromise between partial volume effect and signal-to-noise ratio. The calibration factor was computed accordingly. The calibration quality was monitored over 2.5 years with 33 phantom acquisitions with activities ranging from 7040 to 0.6 MBq. Home-made sources were used to calibrate the well counter. Its reliability was evaluated with activities ranging from 150 to 0.2 kBq measured 34 times over 2.5 years. Results: For the radionuclide calibrator, median [interquartile range] for the error on activity measurement was −0.99 [1.31] %. The optimal SPECT reconstruction parameters were obtained with 16 iterations, 16 subsets and a 12-mm Gaussian post-filter. The calibration factor was 9.87 cps/MBq with an error of −1.05 [2.12] %. The well counter was calibrated with 31.5 cps/kBq, and the error was evaluated to −12.89 [16.55] %. Conclusions: The accuracy and the precision of activity quantification using dedicated quality control were found to be sufficient for use in dosimetry implemented in clinical routine. The proposed methodology could be implemented in other centres to obtain reproducible 177Lu-based treatment dosimetry., SCOPUS: ar.j, info:eu-repo/semantics/published

The purpose of this study was to assess the accuracy and practicality of well counter– and thyroid probe–based methods, commonly available in nuclear medicine facilities, for measuring the concentration of 18F-FDG in blood samples. The degree to which the accuracy of such methods influences quantitative analysis of dynamic PET scans was also assessed. Methods: Thirty-five patients with cancer of the head and neck underwent dynamic PET imaging as part of a study intended to evaluate the utility of quantitative, image-based metrics for assessment of early treatment response. The activity in blood samples from the patients, necessary to provide an estimate of the input function for quantitative analysis, was measured both using a thyroid probe and using a well counter. Three calibration techniques were compared: single-point calibration using a standard solution for the thyroid probe (ProbePoint technique), single-point calibration using a standard solution for the well counter (WellPoint technique), and multiple-point calibration over the full range of expected blood activities for the well counter (WellCurve technique). The WellCurve method was assumed to provide the most accurate estimate of blood activity. The precision of measuring blood volume using a micropipette was also evaluated by obtaining multiple blood samples. Simplified-kinetic-analysis multiple-time-point (SKA-M) uptake rates for the primary tumor were calculated for all 35 patients using PET images and each of the 3 methods for assessing blood concentration. Results: Errors in blood activity measurements ranging from −9.5% to 7.6% were found using the ProbePoint method, whereas the error range was much less (from −1.3% to 0.9%) for the WellPoint method. The precision in blood volume measurements ranged from −6% to 12% in the 10 patients assessed. The errors in blood activity and volume measurements were reflected in the SKA-M measurements in the same range. Conclusion: The WellPoint method provides a compromise between accuracy and clinical practicality. Random errors in both blood activity and volume measurements accumulate and may compromise parameters—such as the SKA-M estimate of tumor uptake rate—that depend not only on images but also on blood concentration data.

The aim of this study is to investigate the outpatient treatment protocol and radiation safety of a new-emerging lutetium-177 ((177)Lu) prostate specific membrane antigen (PSMA) therapy. This work analyzed the dose rate of 23 patients treated with 7400 MBq (177)Lu-PSMA at different distances (0, 0.25, 0.50, 1.0 and 2.0 m) and variable time marks (0, 1, 2, 4, 18, 24, 48 and 120 h) after the termination of infusion. Blood samples were withdrawn from 17 patients within the same group at 3, 10, 20, 40, 60 and 90 min and 2, 3, 24 h after termination of infusion. Seven different patients were asked to collect urine for 24 h and a gamma well counter was used for counting samples. Family members were invited to wear an optically stimulated luminescence dosimeter whenever they were in the proximity of the patients up to 4-5 d. The total dose of the medical team including the radiopharmacist, physicist, physician, nurse, and nuclear medicine technologist was estimated by an electronic personnel dosimeter. The finger dose was determined using a ring thermoluminescent dosimeter for the radiopharmacist and nurse. The mean dose rate at 1 m after 4 h and 6 h was 23 ± 6 μSv h(-1) and 15 ± 4 μSv h(-1) respectively. The mean total dose to 23 caregivers was 202.3 ± 42.7 μSv (range: 120-265 μSv). The radiation dose of the nurse and radiopharmacist was 6 and 4 μSv per patient, respectively, whereas the dose of the physicist and physician was 2 μSv. The effective half life of blood distribution and early elimination was 0.4 ± 0.1 h and 5 ± 1 h, respectively. Seven patients excreted a mean of 45% (range: 32%-65%) from the initial activity in 6 h. Our findings demonstrate that (177)Lu-PSMA is a safe treatment modality to be applied as an outpatient protocol, since the dose rate decreases below the determined threshold of

Background Although NaI(Tl) gamma counters play an important role in many quantitative positron emission tomography (PET) protocols, their calibration for positron-emitting samples has not been standardized across imaging sites. In this study, we characterized the operational range of a gamma counter specifically for positron-emitting radionuclides, and we assessed the role of traceable 68Ge/68Ga sources for standardizing system calibration. Methods A NaI(Tl) gamma counter was characterized with respect to count rate performance, adequacy of detector shielding, system stability, and sample volume effects using positron-emitting radionuclides (409- to 613-keV energy window). System efficiency was measured using 18F and compared with corresponding data obtained using a long-lived 68Ge/68Ga source that was implicitly traceable to a national standard. Results One percent count loss was measured at 450 × 103 counts per minute. Penetration of the detector shielding by 511-keV photons gave rise to a negligible background count rate. System stability tests showed a coefficient of variation of 0.13% over 100 days. For a sample volume of 4 mL, the efficiencies relative to those at 0.1 mL were 0.96, 0.94, 0.91, 0.78, and 0.72 for 11C, 18F, 125I, 99mTc, and 51Cr, respectively. The efficiency of a traceable 68Ge/68Ga source was 30.1% ± 0.07% and was found to be in close agreement with the efficiency for 18F after consideration of the different positron fractions. Conclusions Long-lived 68Ge/68Ga reference sources, implicitly traceable to a national metrology institute, can aid standardization of gamma counter calibration for 18F. A characteristic feature of positron emitters meant that accurate calibration could be maintained over a wide range of sample volumes by using a narrow energy window centered on the 511-keV peak.

Positron emission tomography (PET) has gained widespread use in cancer diagnosis and treatment, but how many malignant cells are required for a tumour to be detected by PET?Three human cancer cell lines [glioblastoma and two subtypes of small cell lung cancer (SCLC)] in concentrations from 10(4) to 10(7) were seeded on six-well plates or plastic tubes and treated with [(18)F]fluorodeoxy-glucose (FDG) in vitro. FDG retention was measured in a PET/CT scanner and in a calibrated well counter. The clinical situation was simulated using a cylinder phantom with a background concentration of FDG.The theoretical detection limit was found to be around 10(5) malignant cells. In a cylinder phantom the detection limit was increased by a factor of 10. The FDG retention by the glioblastoma cell line was significantly higher than the activity of the SCLC cell line. FDG retention measured by PET and a gamma counter was closely correlated to the number of cells and a linear relationship was found.The detection limit of PET is in the magnitude of 10(5) to 10(6) malignant cells. The experimental set-up was robust and well suited as a platform for further investigations of factors influencing the detection limit of PET.

Single-photon-emitting or positron-emitting radionuclides employed in nuclear medicine are detected by using sophisticated imaging devices, whereas simpler detection devices are used to quantify activity for the following applications: measuring doses of radiopharmaceuticals, performing radiotracer bioassays, and monitoring and controlling radiation risk in the clinical environment. Detectors are categorized in terms of function, the physical state of the transducer, or the mode of operation. The performance of a detector is described by the parameters efficiency, energy resolution and discrimination, and dead time. A detector may be used to detect single events (pulse mode) or to measure the rate of energy deposition (current mode). Some detectors are operated as simple counting systems by using a single-channel pulse height analyzer to discriminate against background or other extraneous events. Other detectors are operated as spectrometers and use a multichannel analyzer to form an energy spectrum. The types of detectors encountered in nuclear medicine are gas-filled detectors, scintillation detectors, and semiconductor detectors. The ionization detector, Geiger-Muller detector, extremity and area monitor, dose calibrator, well counter, thyroid uptake probe, Anger scintillation camera, positron emission tomographic scanner, solid-state personnel dosimeter, and intraoperative probe are examples of detectors used in clinical nuclear medicine practice.

SummaryQuantitative positron emission tomography (PET) requires accurate scanner calibration, which is commonly performed using phantoms. It is not clear to what extent this procedure ensures quantitatively correct results in vivo, since certain conditions differ between phantom and patient scans. Aim: We, therefore, have evaluated the actual quantification accuracy in vivo of PET under clinical routine conditions. Patients, methods: We determined the activity concentration in the bladder in patients undergoing routine [18F]FDG whole body investigations with three different PET scanners (Siemens ECAT EXACT HR+ PET: n = 21; Siemens Biograph 16 PET/CT: n = 16; Philips Gemini-TF PET/CT: n = 19). Urine samples were collected immediately after scan. Activity concentration in the samples was determined in well counters cross-calibrated against the respective scanner. The PET (bladder) to well counter (urine sample) activity concentration ratio was determined. Results: Activity concentration in the bladder (PET) was systematically lower than in the urine samples (well The patient-averaged PET to well counter ratios for the investigated scanners are (mean ± SEM): 0.881 ± 0.015 (ECAT HR+), 0.898 ± 0.024 (Biograph 16), 0.932 ± 0.024 (Gemini-TF). These values correspond to underestimates by PET of 11.9%, 10.2%, and 6.8%, respectively. Conclusions: The investigated PET systems consistently underestimate activity concentration in the bladder. The comparison of urine samples with PET scans of the bladder is a straightforward means for in vivo evaluation of the expectable quantification accuracy. The method might be interesting for multi-center trials, for additional quality assurance in PET and for investigation of PET/MR systems for which clear proof of sufficient quantitative accuracy in vivo is still missing.

Background We propose a new approach to facilitate sentinel node biopsy examination by multimodality imaging in which radioactive and near-infrared (NIR) fluorescent nanoparticles depict deeply situated sentinel nodes and fluorescent nodes with anatomical resolution in the surgical field. For this purpose, we developed polyamidoamine (PAMAM)-coated silica nanoparticles loaded with technetium-99m (99mTc) and indocyanine green (ICG). Methods We conducted animal studies to test the feasibility and utility of this dual-modality imaging probe. The mean diameter of the PAMAM-coated silica nanoparticles was 30 to 50 nm, as evaluated from the images of transmission electron microscopy and scanning electron microscopy. The combined labeling with 99mTc and ICG was verified by thin-layer chromatography before each experiment. A volume of 0.1 ml of the nanoparticle solution (7.4 MBq, except for one rat that was injected with 3.7 MBq, and 1 μg of an ICG derivative [ICG-sulfo-OSu]) was injected submucosally into the tongue of six male Wistar rats. Results Scintigraphic images showed increased accumulation of 99mTc in the neck of four of the six rats. Nineteen lymph nodes were identified in the dissected neck of the six rats, and a contact radiographic study showed three nodes with a marked increase in uptake and three nodes with a weak uptake. NIR fluorescence imaging provided real-time clear fluorescent images of the lymph nodes in the neck with anatomical resolution. Six lymph nodes showed weak (+) to strong (+++) fluorescence, whereas other lymph nodes showed no fluorescence. Nodes showing increased radioactivity coincided with the fluorescent nodes. The radioactivity of 15 excised lymph nodes from the four rats was assayed using a gamma well counter. Comparisons of the levels of radioactivity revealed a large difference between the high-fluorescence-intensity group (four lymph nodes; mean, 0.109% ± 0.067%) and the low- or no-fluorescence-intensity group (11 lymph nodes; mean, 0.001% ± 0.000%, p < 0.05). Transmission electron microscopy revealed that small black granules were localized to and dispersed within the cytoplasm of macrophages in the lymph nodes. Conclusion Although further studies are needed to determine the appropriate dose of the dual-imaging nanoparticle probe for effective sensitivity and safety, the results of this animal study revealed a novel method for improved node detection by a dual-modality approach for sentinel lymph node biopsy.

In the course of your day, when you interpret or count a radioimmunoassay or a sample of blood or body fluid, you will probably use a variant of the well counter invented by Hal O. Anger in the early 1950s. If you obtain or read a patient image, it probably came from some type of his gamma camera. If yoy do or see a single photon emission computed tomography study, Hal Anger showed the feasibility. Even if you are working with positrons, some of the early imaging work was done by devices Hal Anger invented. This article deals primarily with the years I spent with Hal, 1962 to 1964. I was fortunate to have the opportunity to spend this time with him when he had just completed the development of his 11-in gamma camera, the first multipurpose camera suitable for diverse clinical examinations. In retrospect, it is easy to see why Hal was honored by the Society of Nuclear Medicine as one of its pioneers and why he was the first recipient of the Ben Cassen Prize. However, it was not always clear that Hal's creative road would lead to such deserved distinction. I have tried to portray the beginnings of this journey to the best of my recollections.

Purpose: Genetic profiling of biopsied tissue is the basis for personalized cancer therapy. However biopsied materials may not contain sufficient amounts of DNA needed for analysis. We propose a method to determine the adequacy of specimens for performing genetic profiling by quantifying metabolic activity. Methods: We measured the response of two radiation detectors to the activity contained in the minimum amount of tumor cells needed for genetic profiling in biopsy specimens obtained under 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) PET/CT guidance. The expected tumor cell concentration in biopsy specimens was evaluated from the amount of DNA needed (∼100 µg) and the number of pathology sections typically used for the analysis. The average 18F-FDG uptake per cell was measured by incubating KPC-4662 pancreatic tumor cells and HT-29 colorectal adenocarcinoma tumor cells in 18F-FDG containing solution (activity concentrations between 0.0122 and 1.51 MBq/mL and glucose concentrations of 3.1 and 1 g/L) for 1 to 1.75 hours and then measuring the activity of a known number of cells. Measurements of surrogate specimens obtained using 18G needle biopsies of gels containing these cells in expected concentrations (∼104 µL−1) were performed using an autoradiography CCD based device (up to 20 min exposure) and a scintillation well counter (∼1 min measurements) about 3 and 5 hours after the end of incubation respectively. Results: At start of autoradiography there were between 0.16 and 1.5 18F-FDG molecules/cell and between 1.14 and 5.43×107 18F-FDG molecules/mL. For the scintillation well counter, sample to minimum-detectable-count rate ratios were greater than 7 and the counting error was less than 25% for ≤80 s measurement times. Images of the samples were identifiable on the autoradiograph for ∼10 min and longer exposure times. Conclusion: Scintillation well counter measurements and CCD based autoradiography have adequate sensitivity to detect the tumor burden needed for genetic profiling in 18G core needle biopsies. Supported in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 and by a sponsored research agreement with Biospace Lab S.A.

We present a calibration method of a clinical SPECT/CT device for quantitative 99mTc SPECT. We use a commercially available reconstruction package including ordered-subset expectation maximization (OSEM) with depth-dependent 3-dimensional resolution recovery (OSEM-3D), CT-based attenuation correction, and scatter correction. We validated the method in phantom studies and applied it to images from patients injected with 99mTc-diphosponate. Methods: The following 3 steps were performed to derive absolute quantitative values from SPECT reconstructed images. In step 1, we used simulations to characterize the SPECT/CT system and derive emission recovery values for various imaging parameter settings. We simulated spheres of varying diameters and focused on the dependencies of activity estimation errors on structure size and position, pixel size, count density, and reconstruction parameters. In step 2, we cross-calibrated our clinical SPECT/CT system with the well counter using a large cylinder phantom. This step provided the mapping from image counts to kBq/mL. And in step 3, correction factors from steps 1 and 2 were applied to reconstructed images. We used a cylinder phantom with variable-sized spheres for verification of the method. For in vivo validation, SPECT/CT datasets from 16 patients undergoing 99mTc-diphosponate SPECT/CT examinations of the pelvis including the bladder were acquired. The radioactivity concentration in the patients9 urine served as the gold standard. Mean quantitative accuracy and SEs were calculated. Results: In the phantom experiments, the mean accuracy in quantifying radioactivity concentration in absolute terms was within 3.6% (SE, 8.0%), with a 95% confidence interval between −19.4% and +12.2%. In the patient studies, the mean accuracy was within 1.1% (SE, 8.4%), with a 95% confidence interval between −15.4% and +17.5%. Conclusion: Current commercially available SPECT/CT technology using OSEM-3D reconstruction, scatter correction, and CT-based attenuation correction allows quantification of 99mTc radioactivity concentration in absolute terms within 3.6% in phantoms and 1.1% in patients with a focus on the bladder. This opens up the opportunity of SPECT quantitation entering the routine clinical arena. Still, the imprecision caused by unavoidable measurement errors is a dominant factor for absolute quantitation in a clinical setup.

A method was developed for the preparation of a standard source to satisfy the U.S. Nuclear Regulatory Commission requirement for calibration of wipe-assay procedures used in nuclear medicine laboratories. An essential element of this standard was that a locally prepared calibration wipe could be used with thin-window Geiger-Muller detectors that detect 99mTc conversion electrons with high sensitivity. This proposed calibration wipe was evaluated with both a NaI(Tl) well counter and a thin-window Geiger-Muller pancake probe. Average detector sensitivities of 1,540 and 160 counts min-1 per 2000 disintegrations min-1, respectively, were found for 99mTc. An analysis of the errors for each step of the procedure showed most to be less than 3% (95% confidence level). The nuclear medicine dose calibrator, used to assay the activity from which the wipe was prepared, was estimated to contribute a 9% absolute calibration error. Use of the pancake probe contributed a 12% geometry-reproducibility error. The total error associated with the use of the calibration wipe standard to calibrate a typical 99mTc wipe-assay procedure, exclusive of the count-dependent error associated with the number of counts acquired, was found for the NaI(Tl) well counter to be given by a percentage of 2 SD = 10% and for the thin-window Geiger-Muller pancake probe, percentage 2 SD = 16%. Coating of the calibration wipe with an acrylic spray, to prevent it from contaminating instruments during use, was evaluated. This coating was effective while it reduced the detectability of the wipe activity by a negligible degree.

Background The use of 90Y for nuclear medicine therapies has steadily increased over the last 10 years. High administered activities are measured in a calibrated re-entrant ionization chamber, while the most sensitive method of assessment of low activities uses a liquid scintillation counter. This method requires the samples to have an acceptably low quench, and therefore heavily coloured samples must undergo chemical processing before assessment. An alternative method has been investigated to measure low activities of 90Y in a sodium iodide well counter by detection of associated Bremsstrahlung. Methods Test samples of 90Y with activities 0.5-730 Bq were measured in a well counter and a liquid scintillation counter, with counting times of 4 h per sample. Both counters were investigated for a relationship between count rate and activity. Results The efficiency of the well counter was found to be 0.08 count x s(-1) x Bq(-1), for a specified vial and sample volume. This is poor compared with the liquid scintillation counter efficiency of 1.0 count x s (-1) x Bq(-1). The uncertainty in measurement of a sample with unknown activity was calculated for a 4 h count time: +/-8.0% at 730 Bq and +/-45% at 6 Bq for the well counter; and +/-8.0% and +/-8.1%, respectively, for the liquid scintillation counter. These errors are dominated by the initial measurement of activity to determine counting efficiency, using a calibrator with an accuracy of +/-8%. If long counting times of both samples and background radiation are practicable, it has been found that a well counter can successfully be used to assess low activities of 90Y.

Nuclear medicine uses a variety of ionization detectors to measure radioactivity attached to pharmaceuticals designed to target specific tissues and even molecules In vivo. The targeting agents include naturally occurring molecules, their engineered variants, and nanostructures. Radioactive labels must emit γ rays (photons) to allow imaging, but beta or alpha emissions are used in radiotherapy of cancer. Both two-dimensional (2D) and three-dimensional (3D) images can be produced. The gamma camera is the most common imaging device with positron emission tomographic (PET) scanners becoming very popular because of their tomographic and quantitative outputs. Hybrid devices using gamma camera and computed tomography (CT) or PET and CT on the same scanning bed have been developed to allow better correlation of regions of elevated radioactivity with physiological structures. Small animal versions of these instruments and their hybrids are available for radiopharmaceutical research studies. Keywords: well counter; gamma camera; SPECT; PET scanner; internal emitter therapy; animal imaging

Attenuation correction is one of the important corrections required for quantitative positron emission tomography (PET). This work will compare the quantitative accuracy of attenuation correction using a simple global scale factor with traditional transmission-based methods acquired either with a small animal PET or a small animal x-ray computed tomography (CT) scanner. Two phantoms (one mouse-sized and one rat-sized) and two animal subjects (one mouse and one rat) were scanned in CTI Concorde Microsystem's MicroPET(R) Focus(TM) for emission and transmission data and in ImTek's MicroCAT(TM) II for transmission data. PET emission image values were calibrated against a scintillation well counter. Results indicate that the scale factor method of attenuation correction places the average measured activity concentration about the expected value, without correcting for the cupping artefact from attenuation. Noise analysis in the phantom studies with the PET-based method shows that noise in the transmission data increases the noise in the corrected emission data. The CT-based method was accurate and delivered low-noise images suitable for both PET data correction and PET tracer localization.

A new type of well-scintillation counter with a double-well and single-plastic scintillator (DW-counter) was developed to simplify time consuming and cumbersome dilution procedures inherent to in-vivo sample measurement. It has the potential to measure many radionuclides which emit a gamma ray or positron. We tested the counting efficiency (CE) of the DW-counter (DCM-200, Aloka Co., Tokyo, Japan) with respect to 6 radionuclides.The outline of DW-counter is altered to a single unit as compared to the prototype, while its basic mechanical constitution was not changed. Six commercially available radionuclides (Tl-201, Tc-99m, I-123, Ga-67, In-111, I-131) were used in this study. For each radionuclide, we prepared two standard solutions containing high (100 MBq/ml) and relatively low radioactivity (10-20 MBq/ml). The radioactivity (Bq) of the radionuclide in each sample at time = 0 was measured with a dose calibrator. Afterwards, it was determined from a decay-time with correction by the physical half-life of each radionuclide. Count rate (cps) of each standard sample was measured in each well ten times per sample. The counting efficiency (CE) of the counter for each radionuclide was determined by measured count rate (cps)/standard radioactivity (Bq) x 100 (%). The conversion constant (CC) which predicts standard radioactivity (Bq) from measured count rate (cps) was obtained as a reciprocal value of the CE.The CE (mean +/- SD) in well-A to Tl-201, Tc-99m, I-123, Ga-67, In-111 and I-131 was 5.90 +/- 0.285%, 8.56 +/- 0.0981%, 8.33 +/- 0.344%, 7.77 +/- 0.15%, 16.4 +/- 0.495% and 10.2 +/- 0.139%, respectively. They were significantly different. The coefficient of variation of the measured count rates was less than 1% in radioactive range higher than 10(3) Bq in well-A and 106 Bq in well-B. The difference in the CE between well-A and -B ranged from 7.614 x 10(2) (I-131) to 9.395 x 10(2) (Tl). The CC ranged from 6.14 (In) to 17.15 (Tl) in well-A and from 5.05057 x 10(3) (In) to 15.83773 x 10(3) (Tl) in well-B. The CE was not significantly affected by a sample volume from 1 to 4 ml in well-A, but showed a slight difference in well-B, which seemed due to a collimation.The measurement error of the DW-counter was less than 1% and the measured count rate (cps) was exactly converted to the standard radioactivity (Bq) by determined CC. The counter is considered useful in the easy evaluation of in-vivo tracer kinetics by avoiding time consuming and cumbersome dilution techniques.

The determination of tissue time–activity course in positron emission tomography is normally performed by the region of interest analysis of reconstructed images. However, in some cases, the same analysis may be performed equally well on the data in sinograms before reconstruction, avoiding the reconstruction of large time sequence data sets, especially important in the 3D mode. Linearization, by remapping the time–activity data, as performed in the Patlak analysis, creates the conditions that enable parameters, estimated pixel-by-pixel in the sinogram data set, to be reconstructed to form parametric images of the influx rate constant and volume of distribution for tracer substances. This chapter presents a general theory and a validation of Patlak analysis for the tracer [ 18 F] fluorodeoxyglucose. Five normal subjects were scanned for 48 min after injection of approximately 200 MBq [ 18 F]fluorodeoxyglucose using a protocol of frames of 3 × 1-minute, 10 × 3-minute, and 3 × 5-minute. During the study, twenty 5 ml blood samples were collected and analyzed for plasma activity concentration. PET measurement is performed on a Siemens ECAT 933/04-16 with seven concurrent acquisition planes resulting in a set of 16 sinograms for each of the planes. Plasma activity is measured using a NaI well counter. The acquired data were back projected using a standard ramp and a Hanning apodizing function with a cutoff at 0.5 cycles per pixel to create cross-sectional slices of the activity concentration distribution for each time frame.

A scintillation counter using a plastic phosphor well is described in which the count rate is satisfactorily independent of a sample volume for 10—410 ml. Its efficiency and sensitivity are some 25 and 2 to 4 times greater, respectively, than for a counter using 32 small G.M. tubes. The use of the counter with 59Fe, 131I, and 51Cr, is discussed with particular reference to both urine and faecal samples and whole-body counting of small animals. It is not suitable at present for double isotope counting.

A scintillation counter is described suitable for the assay of total faecal specimens. Sensitivities are given and are compared with those of a ring of Geiger counters and with those of a conventional sodium-iodide well counter. The assay of mixed isotopes by difference of gamma energy is described.

The incubation time required to attain 90% labeling efficiency (90% radiochemical purity) for technetium Tc 99m labeling of iprofenin (PIPIDA, Diagnostic Isotopes, Inc.), was investigated. Thirty iprofenin vials were prepared according to the manufacturer's instructions. Aliquots were withdrawn from 12 vials at times 0.5, 1, 2, 3, 5, 7, 10, 12, 15, 20, 30, 45, and 60 minutes after mixing. Aliquots were withdrawn from 18 vials at 1, 2, 3, 5, 7, and 10 minutes. Free pertechnetate and reduced/hydrolyzed technetium were isolated from aliquots with instant thin-layer chromatography and quantified with a scintillation well counter. Based on the 30 vials, a mean (+/- S.E.M.) of 5.83 +/- 4.32 minutes was required to attain 90% labeling efficiency. Using tolerance limits calculations, the incubation time required to be assured that 95% of vials have achieved 90% labeling is 16.8 minutes. It is concluded that 99mTc iprofenin vials should be incubated 17 minutes to be assured of 90% labeling efficiency.

Several agents are currently available for blood-pool imaging with positron scintigraphy. Haemoglobin may be labelled with 11 C (T 1 2 20 min ) either by administration of 11CCO by inhalation or by intravenous administration of a sample of the subject's whole blood previously labelled by exposure to 11CCO. Since labelling with 11C requires a particle accelerator, alternative agents labelled with generator-produced 68 Ga (T 1 2 68 min ) would be advantageous. Blood-pool images may be obtained with 68Ga-transferrin following intravenous administration of 68Ga-chloride at acid pH. Recently a method for the preparation of red cells labelled with 68Ga-oxine has been reported. We have compared the three agents, 11C-carboxyhaemoglobin, 68Ga-transferrin and 68Ga-labelled red cells in dogs to assess their relative merits for blood-pool imaging. For 1 h following administration of each agent, periodic blood samples were withdrawn for counting in a NaI (Tl) well counter while conventional two-dimensional images were obtained simultaneously on the Massachusetts General Hospital positron camera. Count rates in regions about the heart, liver and spleen were obtained for each image. The disappearance of blood activity as shown from the results of counting the blood samples and from the counting rate in regions about the heart was found to be identical within experimental error for the three agents. In the liver and spleen regions, the highest count rates were obtained with 68Ga-transferrin and the lowest with 68Ga-labelled red cells; count rates in these regions with labelled red cells were virtually constant throughout the 1 h study. It may be concluded that with the exceptions noted above, the three agents are approximately equivalent for blood-pool imaging.

Quantitative nuclear medicine techniques such as positron emission tomography (PET) require precise and accurate knowledge of both the amount of radioactivity administered to a patient and the radioactivity concentration in blood as a function of time. In addition, the uncertainties in such measurements must be known so that the accuracy and precision of quantitative in vivo metabolic measurements may be estimated. In order to characterize and minimize the measurement errors for PET, well counter and dose calibrator performances were studied over long and short time periods using positron-emitting isotopes. To ensure accurate quantitation with well counters, the use of correction factors for sample volume and high count rate effects is essential. Only small drifts in well counter sensitivity were observed during a 24-h period, but longer-term drifts and poor performance emphasized the need for continuing quality control procedures. Similar behavior was observed for dose calibrators. Dose calibrator, rather than well counter, data should be used for PET imaging instrument calibration. The methods presented have direct application to any quantitative nuclear medicine program.

Foreman [1] suggested in 1953 that a liquid scintillation detector designed specifically to measure radioactivity circulating through the human forearm would be useful in clinical diagnosis. The annular detector, constructed to measure conveniently the human arm in vivo, reduced the number of required photomultiplier tubes without appreciable loss of counting efficiency and minimized the mass of shielding needed for a low background. This detector was found to be an excellent means of measuring radioactivity in the circulation of the arm, and in early trials it also proved to be a facile means of measuring small amounts of radiation in whole mice, rats, or other small animals [2, 3]. It could also be used as a large well counter to assay the radioactivity of 500- to 1000-ml samples of urine, feces, and blood. With most gamma-emitting isotopes in amorphous or variably shaped specimens, effects of thickness were easily minimized by counting all samples of excreta after they were made up to 500 ml in a disposable quart ice-cream carton.