Individualization of Radionuclide Therapies: Challenges and Prospects.

The article presents the problems of clinical implementation of personalized radioisotope therapy. The use of radioactive drugs in the treatment of malignant and benign diseases is rapidly expanding. Currently, in the majority of nuclear medicine departments worldwide, patients receive standard activities of therapeutic radiopharmaceuticals. Intensively conducted clinical trials constantly provide more evidence of a close relationship between the dose of radiopharmaceutical absorbed in pathological tissues and the therapeutic effect of radioisotope therapy. Due to the lack of individual internal dosimetry (based on the quantitative analysis of a series of diagnostic images) before or during the treatment, only a small fraction of patients receives optimal radioactivity. The vast majority of patients receive too-low doses of ionizing radiation to the target tissues. This conservative approach provides "radiation safety" to healthy tissues, but also delivers lower radiopharmaceutical activity to the neoplastic tissue, resulting in a low level of response and a higher relapse rate. The article presents information on the currently used radionuclides in individual radioisotope therapies and on radionuclides newly introduced to the therapeutic market. It discusses the causes of difficulties with the implementation of individualized radioisotope therapies as well as possible changes in the current clinical situation.

Optimized method for normal range estimation of standardized uptake values (SUVmax, SUVmean) in liver SPECT/CT images with somatostatin analog [99mTc]-HYNIC-TOC (Tektrotyd).

BACKGROUND: 99mTc-hydrazinonicotinyl-Tyr3-octreotide ([99mTc]-HYNIC-TOC [Tektrotyd]) is a radiopharmaceutical used for the diagnosis of lesions with overexpression of somatostatin receptors. The purpose of this study was to optimize the method and estimate normal ranges for standardized uptake values of Tektrotyd in healthy livers. MATERIAL AND METHODS: An analysis of standardized uptake value (SUVs) normal ranges was performed for images acquired in a selected "healthy group" of 42 patients evaluated for neuroendocrin tumors. The "pathological group" comprised 20 patients with liver lesions detected by scintigraphic imaging. Normal ranges for radiopharmaceutical uptake values were estimated based on the quantitative analysis of images acquired with a GE Healthcare NM/CT 850 gamma camera. RESULTS: The method for healthy liver segmentation in single photon emission computed tomography/computed tomography (SPECT/CT) was optimized. The normal range of SUVs for the liver was: standardized uptake value body weight (SUVbw) max [5.2-14.0] g/mL and standardized uptake value lean body mass (SUVlbm) [3.5-9.5] g/mL. The relative standard error (relative SE) of activity concentration estimated in the phantom study for the largest hot spheres was: ϕ = 37 mm - 5.9%, ϕ = 28 mm - 7.1%, ϕ = 22 mm - 11.4%, and ϕ = 17 mm - 22%. CONCLUSIONS: Segmentation in the mid-coronal computed tomography (CT) image, at one-fourth of the height of the liver measured from the top, with a medium-sized volume of interest (VOI) outlined on a given transverse SPECT slice was regarded as the optimal method for estimating normal ranges for standardized uptake values. It is necessary to standardize quantification methods in the SPECT/CT studies. Our work is a step forward in obtaining standardization of SPECT/CT SUV calculation methods. Calculations for radiopharmaceutical uptake in tumors with volumes smaller than 5 mL are biased with a significant measurement error.

What validation tests can be done by the clinical medical physicist while waiting for the standardization of quantitative SPECT/CT imaging?

OBJECTIVE: The aim of the study was to assess the accuracy of quantitative SPECT/CT imaging in a clinical setting and to compare test results from two nuclear medicine departments. METHODS: Phantom studies were carried out with two gamma cameras manufactured by GE Healthcare: Discovery NM/CT 670 and NM/CT 850, used in two nuclear medicine departments. The data were collected using a cylindrical uniform phantom and a NEMA/IEC NU2 Body Phantom, filled with 99mTc-pertechnetate. RESULTS: The convergence of activity concentration recovery was validated for the two gamma cameras operating in two medical centers using the cylindrical uniform phantom. The comparison of results revealed a 5% difference in the background calibration factor Bg. cal; 6% difference in COV, and a 0.6% difference in total activity deviation ∆Atot. Recovery coefficients (RCmax) for activity concentration in spheres of the NEMA/IEC NU2 Body Phantom were measured for different image reconstruction techniques. RCmax was in the range of 0.2-0.4 for the smallest sphere (ϕ 10 mm), and 1.3-1.4 for the largest sphere (ϕ 37 mm). Conversion factors for SUVmax and SUVmean for the gamma camera systems used were 0.99 and 1.13, respectively. CONCLUSIONS: (1) Measurements taken in our study confirmed the clinical suitability of 5 parameters of image quality (Bg. cal-background calibration factor, ∆Atot-total activity deviation, COV-coefficient of variation used for image noise assessment, QH-hot contrast, AM-accuracy of measurements, or RC-recovery coefficient) for the validation of SPECT/CT system performance in terms of correct quantitative acquisitions of images. (2) This work shows that absolute SPECT/CT quantification is achievable in clinical nuclear medicine centers. Results variation of quantitative analyses between centers is mainly related to the use of different reconstruction methods. (3) It is necessary to standardize the technique of measuring the SUV conversion factor obtained with different SPECT/CT scanners.

The Epidemiology and Clinical Presentations of Atopic Diseases in Selective IgA Deficiency.

Selective IgA deficiency (sIgAD) is the most common primary immunodeficiency disease (PID), with an estimated occurrence from about 1:3000 to even 1:150, depending on population. sIgAD is diagnosed in adults and children after the 4th year of age, with immunoglobulin A level below 0.07 g/L and normal levels of IgM and IgG. Usually, the disease remains undiagnosed throughout the patient's life, due to its frequent asymptomatic course. If symptomatic, sIgAD is connected to more frequent viral and bacterial infections of upper respiratory, urinary, and gastrointestinal tracts, as well as autoimmune and allergic diseases. Interestingly, it may also be associated with other PIDs, such as IgG subclasses deficiency or specific antibodies deficiency. Rarely sIgAD can evolve to common variable immunodeficiency disease (CVID). It should also be remembered that IgA deficiency may occur in the course of other conditions or result from their treatment. It is hypothesized that allergic diseases (e.g., eczema, rhinitis, asthma) are more common in patients diagnosed with this particular PID. Selective IgA deficiency, although usually mildly symptomatic, can be difficult for clinicians. The aim of the study is to summarize the connection between selective IgA deficiency and atopic diseases.

Physical quantities useful for quality control of quantitative SPECT/CT imaging.

SPECT/CT imaging is transitioning from solely qualitative applications to quantitative analysis. Quantitative SPECT/CT systems require proper calibration, optimization and quality control. Various types of modern SPECT/CT scanners have different software for calibration and quality control (QC). There is still no standardization in this regard for quantitative SPECT/CT. This issue hinders the exchange of obtained results across centers and stunts the development of repeatable and reproducible measurements. The unification and standardization of calibration and quality control techniques for quantitative SPECT/CT systems is currently a pressing need for nuclear medicine departments. The present study presents three selected physical quantities characterizing the quality of quantitative SPECT/CT system and seven quantities, currently used in the literature, to assess the quality of quantitative SPECT/CT images. The measurement of these parameters requires the use of standard gamma camera software for QC, external programs for quantitative analysis of recorded data and clinical software. The authors hope this will help physicists who are willing to perform quantitative SPECT/CT in their departments.

Influence of high tissue-absorbed dose on anti-thyroid antibodies in radioiodine therapy of Graves' disease patients.

BACKGROUND: The results of radioactive iodine (RAI) treatment for Graves' disease (GD) are related to the choice of diagnostic and dosimetry protocols, the steroid protection used, and the subsequent 131I dose. The effect of a high tissue-absorbed dose on the level of anti-thyroid antibodies (ATA) has been rarely considered. OBJECTIVES: To estimate the effect of the first RAI therapy with a dose of 250 Gy on anti-thyreoperoxidase (anti-TPO) and anti-thyroid-stimulating hormone (TSH) receptor thyrotropin receptor antibody - TRAb levels in GD patients. MATERIAL AND METHODS: The analysis encompassed 46 consecutive patients with clinical presentation of GD. We examined the serum levels of TSH, free thyroxine (FT4), anti-TPO, TRAb, thyroid volume (ThV), 131I effective half-life (EHL), introduction of steroid protection, levothyroxine dose used in thyroid replacement therapy - TRT, and effectiveness of treatment. RESULTS: As a result of RAI treatment, hypothyroidism was found in 35 patients (76.1%), euthyroidism in 7 patients (15.2%) and hyperthyroidism in 4 patients (8.7%). After RAI, we observed ThV reduction and increased anti-TPO (p = 0.001 and p = 0.001, respectively). It was found that a shorter EHL correlated with a higher baseline TRAb concentration and lower final anti-TPO serum concentration (p = 0.03 and p = 0.01, respectively). Lower final TRAb was found in patients with steroid protection (p = 0.049). Intergroup comparison of patients without steroid protection showed significantly higher final anti-TPO concentation (p = 0.02). Intergroup comparison of patients with TRT revealed significantly higher final anti-TPO concentration (p = 0.04). CONCLUSIONS: The application of a high absorbed dose of 250 Gy in GD resulted in high efficacy of RAI therapy at 1-year follow-up. An increased ATA level and its relationships with EHL and ThV reduction were observed at 1-year follow-up. There is a possible relationship between steroid protection and anti-TPO concentration.

The diagnostic value of dual-phase SPECT/CT scintigraphy based on transport kinetics of 99mTc-sestamibi confirmed with histopathological findings in patients with secondary hyperparathyroidism - practical consideration.

BACKGROUND: Dual phase 99mTc-sestamibi SPECT/CT preoperative parathyroid scintigraphy (PPS) is seldom discussed in terms of the transport kinetics of the tracer. OBJECTIVES: To assess the relationship between the characteristic type of tracer transport in particular PPS and histopathological findings in patients with secondary hyperparathyroidism (sHPT). MATERIAL AND METHODS: The study comprised 27 patients (13 females and 14 males) with sHPT. Based on tracer accumulation in early phase (EP) and delayed phase (DP), the following types of accumulation for PPS(+) lesions were identified: EP(-)/ DP(+) (type I), EP(+)/DP(+) (type II), EP(+)/DP(-) (type III). EP(-)/DP(-) (type IV) lesions constituted PPS(-) group invisible in SPECT/CT. Overall, 69 lesions 59 PPS(+) and 10 PPS(-) were evaluated histopathologically. RESULTS: Among SPECT/CT PPS(+), types I, II and III occurred in 9 (15%), 49 (83%), and 1 (2%) lesions, respectively. The frequency of histopathological diagnosis of normal and abnormal (APG - adenoma or hyperplasia) parathyroid gland, as well as non-parathyroid (thyroid, lymph nodes, or fat) lesions differed significantly between type I, II, and III lesions (p = 0.036). APG histopathological diagnosis was significantly more frequent in lesions with type II uptake than in lesions with type I uptake (76% vs. 33%, p = 0.0197). Type II lesions had significantly higher odds for histopathological diagnosis of APG or NPG than type IV, PPS(-) lesions [odds ratio = 13.1 (95% CI: 2.75 to 63.27)]. CONCLUSIONS: For SHP patients evaluated with SPECT/CT PPS accumulation type I is a weak premise for surgeon to find parathyroid pathology. Only persistent 99mTc-sestamibi accumulation in both phases - equivocal with accumulation type II - effectively differentiates parathyroid and non-parathyroid lesions as well as indicates with high probability the presence of adenoma or hyperplasia. Type III consistent with washout pattern is rare in sHPT.

SHOULD PERSONNEL OF NUCLEAR MEDICINE DEPARTMENTS USE PERSONAL DOSIMETERS FOR EYE LENS DOSE MONITORING?

Staff at nuclear medicine departments receive doses of ionising radiation higher than the staff of radiotherapy and radiology departments, with the exception of interventional radiologists. Due to the updated lower occupational exposure limit for the lens of the eye, we measured eye exposure in workers of the Nuclear Medicine Department, Pomeranian Medical University in Szczecin, Poland. EYE-D™ dosimeters were used for 3 months by 10 employees working with sources of ionising radiation. Personal dosimeters also measured the exposure of the whole body and hands. The 3-month dose equivalents for the lens of the eye in the employees was 0.20-0.72 mSv. Staff at NMD PMU do not require regular routine eye lens dose monitoring. Eye lens doses were well within the new annual limit of 20 mSv. Doses to the whole body may be used as an indicator of the eye lens doses in the monitored department.

Patient-specific dosimetry of 99mTc-HYNIC-Tyr3-Octreotide in children.

BACKGROUND: Technetium-99m-hydrazinonicotinamide-Tyr3-octreotide (99mTc-HYNIC-TOC) is recognized as a promising radiopharmaceutical for diagnosing neuroendocrine tumors (NETs). However, 99mTc-HYNIC-TOC dosimetry has been investigated only for adults. As pediatric radionuclide therapies become increasingly common, similar dosimetric studies for children are urgently needed. The aim of this study is to report personalized image-based biodistributions and dosimetry evaluations for children studies performed using 99mTc-HYNIC-TOC and to compare them with those from adult subjects. Eleven children/teenage patients with suspected or diagnosed NETs were enrolled. Patient imaging included a series of 2-3 whole-body planar scans and SPECT/CT performed over 2-24 h after the 99mTc-HYNIC-TOC injections. The time-integrated activity coefficients (TIACs) were obtained from the hybrid planar/SPECT technique. Patient-specific doses were calculated using both the voxel-level and the organ-level approaches. Estimated children doses were compared with adults' dosimetry. RESULTS: Pathologic uptake was observed in five patients. TIACs for normal organs with significant uptakes, i.e., kidneys, spleen, and liver, were similar to adults' TIACs. Using the voxel-level approach, the average organ doses for children were 0.024 ± 0.009, 0.032 ± 0.017, and 0.017 ± 0.007 mGy/MBq for the kidneys, spleen, and liver, respectively, which were 30% larger than adults' doses. Similar values were obtained from the organ-level dosimetry when using OLINDA with adapted organ masses. Tumor doses were 0.010-0.024 mGy/MBq. However, cross-organ contributions were much larger in children than in adults, comprising about 15-40% of the total organ/tumor doses. No statistical differences were found between mean doses and dose distributions in patients with and without pathologic uptakes. CONCLUSION: Although the children TIACs were similar to those in adults, their doses were about 30% higher. No significant correlation was found between the children's doses and their ages. However, substantial inter-patient variability in radiotracer uptake, indicating disparity in expression of somatostatin receptor between different patients, emphasizes the importance and necessity of patient-specific dosimetry for clinical studies.

Semi-quantitative method for the assessment of focal lesions in parathyroid scintigraphy with relation to histopathology: a prospective study.

BBACKGROUND: The aim of this paper was to analyse our own semi-quantitative method of assessing focal lesions localised in pre-operative diagnostic scintigraphy of primary hyperparathyroidism (PHPT) using 99mTc-MIBI with washout and comparing these data with the result of the histopathological examination (HP). MATERIAL AND METHODS: A total of 40 (37 female, 3 male, average age 58.7 years) patients with a suspicion of PHPT were enrolled for prospective analysis. Dual phase planar and SPECT/CT examination with 99mTc-MIBI were performed. The tumour to background ratios in the 10th and 120th minute were calculated (TBR10 and TBR120) on the basis of the planar acquisition. PTH, ionised calcium and phosphate levels were measured. Parathyroid surgery alone or combined with subtotal/total thyreoidectomy was conducted in 23 (57.5%) and 17 (42.5%) patients, respectively. A HP was performed in all patients. RESULTS: Average concentration of PTH in the whole group was 243.95 pg/ml. There was a statistically significant correlation between medians of PTH concentration and parathyroid histopathological results (p = 0.01). A total of 45 lesions of increased uptake were found in 32 (80.0%) and 34 (85%) patients in the early phase and the delayed phase, respectively. The post-operative material contained 20 (44.5%) parathyroid adenomas, 11 (24.5%) cases of hyperplasia, 2 (4.4%) cancers, 4 (8.9%) cases of normal parathyroid tissue, 2 (4.4%) lymph nodes and 6 (13.3%) cases of thyroid gland tissue. The medians of TBR10 and TBR120 for lesions examined in the HP were respectively: 3.64 and 2.59 for adenoma; 3.08 and 2.18 for hyperplasia; 7.7 and 5.5 for parathyroid cancer, 4.89 and 3.16 for normal tissue and 5.26 and 2.95 for lymph nodes or thyroid gland tissue. A high correlation coefficient of TBR10 to TBR120 in the parathyroid adenoma and parathyroid hyperplasia groups was observed with r = 0.867 and r = 0.964, respectively. The ρr correlation coefficient of TBR10 to TBR120 for normal parathyroid was 0.4. There was a statistically significant association between the HP and TBR10 medians (p = 0.047), but not between histopathology and TBR120 medians (p = 0.840). CONCLUSIONS: The washout technique in pre-operative 99mTc-MIBI scintigraphy is effective in detecting lesions of the parathyroid (cancer, adenoma, hyperplasia, normal tissue of the parathyroid). Parathyroid cancers in semi-quantitative analysis were characterised by a slightly higher TBR. However, it is impossible to differentiate lesions based on this data. Histopathology results are significantly associated with TBR and PTH.

[The reference of normal values of the sacroiliac joint index in bone scintigraphy].

Introduction: Scintigraphy of sacroiliac joints as functional imaging provides unique information on the existing disease process. By using radiopharmaceuticals that allow imaging of the metabolic activity within the joint, it is possible to assess the stage of the disease, even when there are no lesions in radiological images. Quantitative analysis of scintigrams of sacroiliac joints is performed by comparing the uptake in both of them in relation to the uptake in the sacral bone area. The values of sacroiliac (SI/S) indices are influenced by the age of the patient, sex, state of health, and a range of individual biological features. Therefore, reference values of SI/S ratios are very important for medical specialists who describe and diagnose locomotor system diseases. The aim of this paper is to develop a reference range of sacroiliac ratios. The innovativeness of this paper involves examining sacroiliac ratios for various age groups, in children and adult patients, taking their sex into consideration. Materials and methods: The study comprised a group of 335 people with proper bone scintigraphy. These people were divided into children and patients aged ≥21. Children were divided into 4 age groups (1­5; 6­10; 11­15; 16­20) and adults into 6 age groups (21­30; 31­40; 41­50; 51­60; 61­70; ≥71). Sacroiliac ratios were calculated using the method of three rectangular region of interests located on the left and right sacroiliac joint and on the sacral bone. The sacroiliac ratio was calculated for both joints by dividing the average number of counts within a selected sacroiliac joint by the average number of counts within the sacral bone. Results: SI/S borderline reference values covered the range of 1.18÷2.28 that was obtained for children aged ≤5 and for the group of 11­15-year-olds. Considerable discrepancies in the values of the coefficient for women and men were seen among 31­50-year-olds. Conclusions: Borderline reference results for the entire control group cover the range of 1.18 ±2.28. The lower reference value applies to ≤5-year-olds, whereas the higher value applies to the group of 11­15-year-olds. The standard deviation value obtained was highest in paediatric patients. The results indicate the occurrence of significant individual differences between patients in this age group.

Evaluation of dead-time corrections for post-radionuclide-therapy (177)Lu quantitative imaging with low-energy high-resolution collimators.

OBJECTIVES: Dead-time (DT) effects rarely cause problems in diagnostic single-photon emission computed tomography (SPECT) studies; however, in post-radionuclide-therapy imaging, DT can be substantial. Therefore, corrections may be necessary if quantitative images are used in image-based dosimetry or for evaluation of therapy outcomes. This task is particularly challenging if low-energy collimators are used. Our goal was to design a simple method to determine the dead-time correction factor (DTCF) without the need for phantom experiments and complex calculations. METHODS: Planar and SPECT/CT scans of a water phantom containing a 70 ml bottle filled with lutetium-177 (Lu) were acquired over 60 days. Two small Lu markers were used in all scans. The DTCF based on the ratio of observed to true count rates measured over the entire spectrum and using photopeak primary photons only was estimated for phantom (DT present) and marker (no DT) scans. In addition, variations in counts in SPECT projections (potentially caused by varying bremsstrahlung and scatter) were investigated. RESULTS: For count rates that were about two-fold higher than typically seen in post-therapy Lu scans, the maximum DTCF reached a level of about 17%. The DTCF values determined directly from the phantom experiments using the total energy spectrum and photopeak counts only were equal to 13 and 16%, respectively. They were closely matched by those from the proposed marker-based method, which uses only two energy windows and measures photopeak primary photons (15-17%). CONCLUSION: A simple, marker-based method allowing for determination of the DTCF in high-activity Lu imaging studies has been proposed and validated using phantom experiments.

Radiation doses of employees of a Nuclear Medicine Department after implementation of more rigorous radiation protection methods.

The appropriate radiation protection measures applied in departments of nuclear medicine should lead to a reduction in doses received by the employees. During 1991-2007, at the Department of Nuclear Medicine of Pomeranian Medical University (Szczecin, Poland), nurses received on average two-times higher (4.6 mSv) annual doses to the whole body than those received by radiopharmacy technicians. The purpose of this work was to examine whether implementation of changes in the radiation protection protocol will considerably influence the reduction in whole-body doses received by the staff that are the most exposed. A reduction in nurses' exposure by ~63 % took place in 2008-11, whereas the exposure of radiopharmacy technicians grew by no more than 22 % in comparison with that in the period 1991-2007. Proper reorganisation of the work in departments of nuclear medicine can considerably affect dose reduction and bring about equal distribution of the exposure.

Personalized image-based radiation dosimetry for routine clinical use in peptide receptor radionuclide therapy: pretherapy experience.

Patient-specific dose calculations are not routinely performed for targeted radionuclide therapy procedures, partly because they are time consuming and challenging to perform. However, it is becoming widely recognized that a personalized dosimetry approach can help plan treatment and improve understanding of the dose-response relationship. In this chapter, we review the procedures and essential elements of an accurate internal dose calculation and propose a simplified approach that is aimed to be practical for use in a busy nuclear medicine department.

Prognostic value of myocardial perfusion scintigraphy for patients suspected of and diagnosed with coronary artery disease.

BACKGROUND: The prognostic value of myocardial perfusion scintigraphy (MPS) continues to attract interest and provoke discussions.This study was an attempt to investigate the methods. OBJECTIVE: Determination of the prognostic value of MPS for patients suspected of and diagnosed with coronary artery disease (CAD). MATERIAL AND METHODS: The study group included 215 patients, 134 males and 81 females, aged 21-66, mean age 48. Tc-99m-MIBI myocardial perfusion scintigraphy was performed and information concerning the diagnosis, aim of the examination, past coronary episodes, clinical condition, duration and type of complaints, concomitant diseases, test results, revascularisation procedures and pharmacological treatment was gathered. Further history of the patients was monitored throughout the observation period of 52 months on average. The patients were divided into the following two groups: Group I - suspected coronary artery disease: 124 patients aged 21-65,59 males and 65 females; Group II - diagnosed coronary artery disease: 91 patients aged 31-66, 75 males and 16 females diagnosed with CAD, including 39 s/p myocardial infarct, 31s/p infarct and revascularisation, 21 s/p revascularisation. The probability of CAD was calculated using the Diamond method for the patients suspected of CAD. The obtained results were examined in a statistical analysis. RESULTS: Normal MPS results were obtained for 94/124 patients suspected of CAD, 15/91 patients diagnosed with CAD,64/81 females and 45/134 males. In Group I, apart from pathological MPS results, reversible ischemia was determined in as many as 27/30 patients, and only 17/91 patients in Group II. No patients with normal MPS results suffered major cardiac events,only one of them underwent revascularisation. Major cardiac events occurred in the case of patients with pathological MPS results: Group I - 2 myocardial infarcts and 2 cardiac deaths,Group II - 3 infarcts and 10 cardiac deaths. Minor cardiac events, apart from one case, were also only observed in the case of patients with pathological MPS results: Group I - 10 revascularisations and one case of unstable CAD, Group II- 12 revascularisations and 7 cases of unstable CAD. Patients with normal MPS results and stenosis in coronary angioraphy suffered no cardiac events. Cardiac events occur mostly in the group with a medium and high risk of CAD and in the case of patients diagnosed with CAD. CONCLUSIONS: 1. Normal MPS results for patients suspected of or diagnosed with CAD: s/p infarct and/or CABG prognosticate a mild course of the disease, without or with a minimal number of cardiac events, also in a longer observation period.2. Pathological MPS results clearly imply a greater risk of cardiac events, and the number of events increases with the greater probability of CAD and with the patient's age. 3. Normal MPS results, even with significant stenosis in coronary angiography,prognosticate a low risk of cardiac events.

The accuracy and reproducibility of SPECT target volumes and activities estimated using an iterative adaptive thresholding technique.

OBJECTIVE: Our aim was to design a practical and reproducible image segmentation method for calculations of total absorbed doses in organs and tumours for internally delivered radioisotopes. We have built upon our previously proposed use of two separate thresholds and employed an iterative technique for semiautomatic selection of background regions for segmenting an object of interest using thresholds that depend on the source-to-background ratio of activity concentrations. METHODS: The parameters of curves relating volume and activity thresholds to source-to-background ratio were established using phantoms with 20 different inserts. The accuracy of our technique was validated using a second phantom experiment, whereas the reproducibility of volume, activity and dose estimates of organs and tumours was investigated using 13 patient studies. The accuracy and reproducibility of segmentations achieved were assessed using images reconstructed with three different methods that ranged from a standard clinical reconstruction to an advanced quantitative reconstruction approach. RESULTS: In the validation phantom experiment, bottle volumes and activities measured using iterative adaptive thresholding agreed on average with the true values to within 4%, regardless of the reconstruction method used. In the patient studies, volumes and activities estimated from the single-photon emission computed tomography images reconstructed with clinical software agreed with the volumes and activities estimated using the advanced reconstruction approach to within 6%, whereas the corresponding doses agreed to within 4%. CONCLUSION: The proposed iterative adaptive thresholding technique can accurately determine object volume and activity, which allows standard clinical reconstructions to generate absorbed dose estimates that are similar to those values obtained using more advanced reconstruction methods.

Dynamic renal scintigraphy with 99mTc-DTPA for the assessment of renal function after therapy of acute lymphoblastic leukemia in children.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) and its treatment may lead to impairment of kidney function. The aim of the present study was to evaluate kidney function in children after treatment of ALL. We used our 99mTc-DTPA (diethylene triamine pentaacetic acid labeled with 99mTc) dynamic scintigraphy protocol. MATERIAL AND METHODS: The study group consisted of 48 ALL patients, aged 79-275 months, in complete remission (mean duration 51 months). Treatment was according to the guidelines of the Berlin Frankfurt Münster (BFM) BFM 86 and BFM 90 protocols in 36 (75%) and 12 (25%) children, respectively. Follow-up after treatment was up to 12 months in 10 (21%) children (group I), 12-60 months in 21 (44%) children (group II), and more than 60 months in 17 (35%) children (group III). 99mTc-DTPA dynamic renal scintigraphy was done in all patients. The glomerular filtration rate (GFR) was determined according to Gates and the diuretic test was done after 18 minutes of the examination. RESULTS: The glomerular filtration rate at the end of the 5-year follow-up was less than 80 mL/min/1.73 m2 (p < 0.002) in 3 (25%) children treated with the BFM 86 protocol. In the remaining 45 (94%) patients, GFR exceeded 80 mL/ min/1.73 m2. Normal renogram curves were obtained in 40 (83%) patients. Eight (17%) children had cumulative curves with normal clearance. This finding was interpreted as non-obstructive uropathy. There was no statistical correlation between outflow disorders seen during dynamic scintigraphy, type of chemotherapy protocol, and assignment to risks group. CONCLUSIONS: 1. There was no clinically significant kidney function impairment in children after treatment of ALL. 2. Dynamic renal scintigraphy can be a valuable and non-invasive method for the assessment of kidney function in patients with a risk factor in the form of previous potentially nephrotoxic antitumor treatment.

Patient-specific radiation dosimetry of 99mTc-HYNIC-Tyr3-octreotide in neuroendocrine tumors.

UNLABELLED: (99m)Tc-hydrazinonicotinamide-Tyr(3)-octreotide ((99m)Tc-HYNIC-TOC) is increasingly gaining acceptance as a new radiopharmaceutical for the diagnosis of pathologic lesions overexpressing somatostatin receptors. However, little information has been published about the radiation dosimetry of this agent. The aim of this study was to assess the biodistribution and radiation dosimetry of commercially available (99m)Tc-HYNIC-TOC. A dose calculation procedure designed to be feasible to implement in a busy clinical environment was used. METHODS: Twenty-eight patients were imaged for suspected neuroendocrine tumors using a series of whole-body planar, dynamic planar, and SPECT/CT studies, after injection with (99m)Tc-HYNIC-TOC. Patient-specific dosimetry was performed using the OLINDA/EXM software with time-integrated activity coefficients estimated from a hybrid planar/SPECT technique. A phantom experiment was performed to establish adaptive thresholds for determination of source region volumes and activities. RESULTS: Pathologic uptake, diagnosed as due to neuroendocrine tumors, was observed in 12 patients. Normal organs with significant uptake included the kidneys, liver, and spleen. The mean effective dose after (99m)Tc-HYNIC-TOC injection was 4.6 ± 1.1 mSv. Average normal-organ doses were 0.030 ± 0.012, 0.021 ± 0.007, and 0.012 ± 0.005 mGy/MBq for the spleen, kidneys, and liver, respectively. The interpatient kidney dose ranged from 0.011 to 0.039 mGy/MBq, whereas the range of tumor doses varied from 0.003 to 0.053 mGy/MBq. The ratio of tumor to kidney dose ranged from 0.13 to 2.9. The optimal thresholds for recovery of true activity in the phantom study were significantly lower than those used for volume determination. CONCLUSION: The patient-specific 3-dimensional dosimetry protocol used in this study is a clinically feasible technique that has been applied to demonstrate large dose variations in tumors and normal organs between patients imaged with (99m)Tc-HYNIC-TOC.

Static renal scintigraphy with 99mTc-DMSA for the assessment of renal damage after therapy for acute lymphoblastic leukemia in children.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) and its treatment may adversely affect kidney function. The aim of the present study was to determine whether 99mTc-DMSA static renal scintigraphy can be used to disclose kidney damage at the end of therapy for ALL in children. MATERIAL AND METHODS: The study group consisted of 48 ALL patients aged 6.6-22.9 years, with a mean time of continuous complete remission of 51 months. Static renal scintigraphy with 99mTc-DMSA was performed in all patients. RESULTS: Minor scars in the renal cortex were diagnosed with scintigraphy in 6 (13%) patients. A significant correlation was found between renal scarring and a history of urinary tract infection. CONCLUSIONS: No clinically significant kidney damage was found after completion of treatment of ALL. Static renal scintigraphy may be a valuable noninvasive method for visualization of renal cortex pathology.