Dual Tracer 99mTc-Pertechnetate/99mTc-MIBI Dual-Time-Point SPECT/CT Parathyroid Gland Assessment Regarding to Parathyroid Gland Size and Biochemical Parameters - Two Years Single Imaging Centre Experience.

INTRODUCTION: Preoperative parathyroid imaging is inevitable part of focused parathyroid surgery. The aim of our study was assessment of parathyroid scintigraphy diagnostic accuracy regarding to size and metabolic parameters of hyperfunctioning parathyroid tissue. MATERIAL AND METHODS: Parathyroid scintigraphy for suspected primary hyperparathyroidism was performed in 95 patients during years 2015 and 2016. Of them, 75 patients with known clinical outcome (40 underwent surgery, 35 had documented laboratory follow-up) were further retrospectively evaluated. The performance of dual tracer 99mTc-pertechnetate and 99mTc-MIBI subtraction and dual-time-point 99mTc-MIBI imaging with SPECT/CT was analysed. Serum parathyroid hormone (PTH), calcaemia, ionized calcaemia and phosphataemia and ultrasound detected adenoma volume and largest diameter in false negative and true positive findings were compared using Mann-Whitney test. RESULTS: Sensitivity and specificity of parathyroid scintigraphy was 74.5% and 95.8%, respectively. NPV was 63.8% and PPV 97.4%. Hyperfunctioning parathyroid tissue detectability was almost significantly associated with hypophosphataemia and PTH levels. CONCLUSION: Parathyroid scintigraphy provides high sensitivity and superior specificity in parathyroid adenoma location, nevertheless the diagnostic accuracy tends to decline in smaller adenomas and in less metabolically active parathyroid tissue causing only subtle biochemical changes. 18F-Fluorocholine PET/CT or 3D SPECT/CT subtraction should be a reasonable option for those cases.

Highly Effective Radioisotope Cancer Therapy with a Non-Therapeutic Isotope Delivered and Sensitized by Nanoscale Coordination Polymers.

Nuclear medicine with radioisotopes is extremely useful for clinical cancer diagnosis, prognosis, and treatment. Herein, polyethylene glycol (PEG)-modified nanoscale coordination polymers (NCPs) composed of hafnium (Hf4+) and tetrakis (4-carboxyphenyl) porphyrin (TCPP) are prepared via a one-pot reaction. By chelation with the porphyrin structure of TCPP, such Hf-TCPP-PEG NCPs could be easily labeled with 99mTc4+, an imaging radioisotope widely used for single-photon emission computed tomography (SPECT) in a clinical environment. Interestingly, Hf, as a high- Z element in such 99mTc-Hf-TCPP-PEG NCPs, could endow nontherapeutic 99mTc with the therapeutic function of killing cancer cells, likely owing to the interaction of Hf with γ rays emitted from 99mTc to produce charged particles for radiosensitization. With efficient tumor retention, as revealed by SPECT imaging, our 99mTc-Hf-TCPP-PEG NCPs offer exceptional therapeutic results in eliminating tumors with moderate doses of 99mTc after either local or systemic administration. Importantly, those biodegradable NCPs could be rapidly excreted without much long-term body retention. Our work, showing the success of applying NCPs for radioisotope therapy (RIT), presents a potential concept for the realization of highly effective cancer treatment with 99mTc, a short-half-life (6.0 h) diagnostic radioisotope, which is promising for cancer RIT with enhanced efficacy and reduced side effects.

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.

Prognostic value of (99m)Tc-pertechnetate thyroid scintigraphy in radioiodine therapy in a cohort of Chinese Graves' disease patients: a pilot clinical study.

OBJECTIVES: This study is to assess the prognostic value of (99m)Tc-pertechnetate thyroid scintigraphy for predicting the outcomes of fixed low dose of radioiodine therapy (RIT) in a cohort of Chinese Graves' disease (GD) patients. MATERIALS AND METHODS: This is a retrospective study of GD patients who received RIT with a single dose of radioiodine (5 mCi). All the patients received (99m)Tc-pertechnetate thyroid scintigraphy prior to RIT. Thyroid mass, (99m)Tc-pertechnetate uptake, gender, age at diagnosis, duration of the disease, ophthalmopathy, and serum levels of FT4, FT3, TT4, and TT3 prior to RIT were analyzed as potential interference factors for outcomes of RIT. RESULTS: One hundred and eighteen GD patients who completed RIT were followed up for 12 months. The outcomes (euthyroidism, hypothyroidism, and hyperthyroidism) were found to be significantly associated with thyroid mass and (99m)Tc-pertechnetate uptake. Patients with thyroid mass ≤ 40.1 g or (99m)Tc-pertechnetate uptake ≤ 15.2% had higher treatment success. CONCLUSIONS: A fixed low dose of 5 mCi radioiodine seems to be practical and effective for the treatment of Chinese GD patients with thyroid mass ≤ 40.1 g and (99m)Tc-pertechnetate uptake ≤ 15.2%. This study demonstrates (99m)Tc-pertechnetate thyroid scintigraphy is an important prognostic factor for predicting the outcomes of RIT.

Technetium-99m-labeled anti-EGF-receptor antibody in patients with tumor of epithelial origin: I. Biodistribution and dosimetry for radioimmunotherapy.

UNLABELLED: Accurate estimation of biodistribution and absorbed dose to normal organs and tumors is important for immunoscintigraphic studies and radioimmunotherapy treatment planning. METHODS: Four patients (3 men, 1 woman; mean age 54.8 +/- 9.2 yr; range 42-64 yr) were administered 3 mg of anti-human epidermal growth factor receptor (anti-hEGF-r) antibody (ior egf/r3), radiolabeled with 99mTc activity of 39.5 +/- 1.1 mCi (range 38.5 mCi-40.7 mCi) by intravenous bolus infusion. After administration, blood and urine samples were collected from three patients up to 24 hr after injection. Whole-body anterior and posterior scans were obtained at 5 min and 1, 3, 5 and 24 hr after injection. Using a computer program, regions of interest were drawn over the heart, liver, spleen, bladder and tumor to measure the activity in the source organs at each scanning time. Time-activity curves for each source organ were then fitted to monoexponential or biexponential functions by nonlinear least squares regression using the flexible polyhedrals method, which adequately fit our data with the correlation coefficient of 0.985 +/- 0.013, and were integrated to determine organ residence times. The mean absorbed doses to the whole body and various normal organs were then estimated from residence times and from blood and urine samples using the methods developed by the Medical Internal Radiation Dose Committee. The effective dose equivalent and effective dose were calculated as prescribed in ICRP Publication Nos. 30 and 60. RESULTS: Plasma disappearance curves of 99mTc-labeled anti-hEGF-r antibody were best-fit by a two-compartment model in all patients with a distribution half-life (t(1/2alpha)) of 0.207 hr +/- 0.059 hr (mean +/- s.d., n = 3) and an elimination half-life (t(1/2beta)) of 13.9 hr +/- 2.2 hr. Among the various organs, significant accumulation of the radiolabeled antibody was found in the liver (48.5% +/- 4.4%, mean +/- s.d.), heart (3.50% +/- 0.17%) and spleen (3.1% +/- 1.8%) at 5 min postadministration. These values were reduced to 3.2% +/- 0.4%, 0.1% +/- 0.01% and 0.1% +/- 0.1%, respectively, at 24 hr. Mean cumulative urinary excretion of 99mTc-labeled anti-hEGF-r antibody was 4.6% +/- 0.6% at 24 hr postinjection. Estimates of radiation absorbed dose to normal organs in rad/mCi administered (mean +/- s.d., n = 4) were: whole body 0.017 +/- 0.002; gallbladder wall 0.074 +/- 0.007; spleen 0.136 +/- 0.076; and liver 0.267 +/- 0.036. The effective dose equivalent and effective dose estimates for adults were 0.041 +/- 0.008 rem/mCi and 0.027 +/- 0.004 rem/mCi administered. CONCLUSION: This feasibility study indicates that 99mTc-labeled anti-hEGF-r antibody (ior egf/r3) can be used safely; this analysis provides a dosimetric framework for future studies. This monoclonal antibody, labeled with 188Re, could possibly permit a successful regional radioimmunotherapy of tumors of epithelial origin.

Preoperative imaging in primary hyperparathyroidism. Role of thallium-technetium subtraction scintigraphy.

Primary hyperparathyroidism, although often silent clinically, may lead to significant morbidity if it remains untreated. In more than 95% of all cases the cause is a parathyroid adenoma or glandular hyperplasia. Regression of disease follows successful surgical excision of the abnormal parathyroid gland. Recurrent or persistent hyperparathyroidism is most commonly caused by solitary adenomas, which may have an ectopic location. Preoperative localization of lesions may improve postoperative cure rates and decrease morbidity. Thallium T1 201 chloride-technetium Tc 99m pertechnetate subtraction scintigraphy was performed on 15 patients with primary hyperparathyroidism. The sensitivity and specificity for detection of abnormal glands were 90% and 95%, respectively. False-positive or false-negative results were minimize by strict adherence to a protocol and by the use of well-defined diagnostic criteria. Because of the superior sensitivity and specificity, this modality should be the primary imaging method of choice for preoperative evaluation of primary hyperparathyroidism. The relative role of other imaging modalities is also discussed.

The 1-month outcome of patients with a low probability Technegas ventilation/perfusion lung scan.

The objective was to study the 1-month outcome of patients who had a low probability ventilation/perfusion lung scan using Technegas radioaerosol as the inhalational agent and who did not receive anticoagulation. One hundred consecutive patients with suspected pulmonary embolism were studied retrospectively. Their Technegas lung scans were classified by two blinded and independent nuclear medicine physicians and the medical records of all patients with a low probability scan were reviewed. One hundred inpatients (42 males and 58 females) with a mean age of 63 years were studied. The three most common clinical presentations leading to lung scintigraphy were unexplained dyspnoea (30 cases), unexplained dyspnoea with pleuritic chest pain (26 cases) and pleuritic chest pain only (15 cases). Nine patients had been judged by their managing medical team to have a high clinical probability of true pulmonary embolism, 32 had an intermediate probability clinical presentation and 59 a low clinical probability of pulmonary embolism. None of the 100 patients experienced further episodes of suspected or proven pulmonary embolism during the follow-up period. Six patients died. In none of them was pulmonary embolism either the cause of or a major contributing factor to death. The finding of a low probability scan using Technegas as the ventilation scintigram agent of choice describes a group of patients who, even in the absence of therapeutic anticoagulation, have a favourable 1-month outcome free of either true or suspected clinical pulmonary embolism. Invasive, pulmonary angiography-based diagnostic strategies may not be needed in this group of patients.

Pharmacokinetics of 99Tcm-pertechnetate and 188Re-perrhenate after oral administration of perchlorate: option for subsequent care after the use of liquid 188Re in a balloon catheter.

Radioactive wires and other linear sources are currently being used in clinical trials as endovascular brachytherapy to prevent restenosis after percutaneous transluminal coronary angioplasty. A new concept is the use of a liquid-filled balloon containing a beta-emitting radioisotope. A major advantage is optimal delivery of the radioactivity to the vessel wall. Rhenium-188 (188Re) is a high-energy beta-emitter that is routinely available from a 188W/188Re generator in liquid form. Since 188Re-perrhenate could be released in the unlikely event of balloon rupture, we investigated whether, in analogy to pertechnetate, subsequent use of perchlorate can reduce the uptake of perrhenate in the thyroid. We performed static (n = 9) and dynamic (n = 11) thyroid scintigraphy with 99Tcm-pertechnetate to estimate the overall reduction in activity within 30 min and the washout from the thyroid after oral administration of 600 mg perchlorate (T1/2). In two patients, 188Re was injected to estimate the whole-body distribution and the discharge of thyroid activity after perchlorate use. Based on MIRD Dose Estimate Report No. 8 (valid for 99Tcm-pertechnetate), the radiation burden was calculated for intravenous administration of 188Re and competitive blocking with perchlorate. In 20 patients, 99Tcm uptake by the thyroid was reduced by 85% within 30 min by perchlorate. The mean (+/- S.D.) washout rate (T1/2) was 8 +/- 2 min in 11 patients. Perrhenate showed a whole-body distribution similar to that of pertechnetate and the thyroid activity could be displaced (T1/2 = 6.3 and 9.3 min, respectively) by oral administration of perchlorate, with reductions in uptake of 83% and 75% within 30 min, respectively. Whole-body scanning demonstrated no regional accumulation of 188Re-perrhenate with excretion by urine. Dose estimates gave an effective dose equivalent of 0.42 mSv MBq-1, which decreased to 0.16 mSv MBq-1 after perchlorate blocking. 188Re has favourable properties for endovascular brachytherapy via a balloon catheter and, in the unlikely event of balloon rupture, whole-body radiation can be reduced to 38% by subsequent oral administration of perchlorate.

The value of Tc-99m tetrofosmin thyroid scintigraphy in patients with nodular goiter.

The aim of this study is to investigate the value of Tc-99m tetrofosmin (Tc-99m-TF) in conjunction with conventional Tc-99m-pertechnetate (Tc-99m-P) scintigraphy in the differentiation of malignant nodules from benign thyroid nodules. Forty-two patients [(32 females, 10 males; mean age 41 +/- 13 years; twenty-two multinodular goiter (MNG) patients with 58 nodules and 20 solitary thyroid nodules (STN)] were included in the study. Thyroid scintigraphy with Tc-99m-P and Tc-99m-TF, thyroid ultrasonography and fine needle aspiration cytology (FNAC) were performed. After i.v. injection of 370-550 MBq Tc-99m-TF, images were obtained at 15 minutes and evaluated semiquantitatively by using a five point (0-4) scoring system. Four patients with a hypoactive STN, and 1 patient with a hypoactive MNG was found to have thyroid malignancy by histopathological examination; 2 of these patients had false negative benign FNAC results. The tetrofosmin uptake score (TUS) was 2-3-3-3 and 3 in these 5 malignant nodules. Five hyperactive (hot or warm) STN with benign FNAC had a TUS of 2-3-3-3-3. All hypoactive (cold) MNG nodules with benign FNAC (n = 21) had TUS < or = 2. Our preliminary results suggest that follicular adenomas and thyroid cancers have higher tetrofosmin uptake than benign colloidal goiter nodules. Mitochondrial sequestration of tetrofosmin in benign or malignant follicular cells that proliferate more rapidly than normal follicular cells and/or hypervascularity may be responsible for this. The use of Tc-99m-TF in conjunction with Tc-99m-P thyroid scintigraphy will be helpful in the evaluation of patients with nodular goiter (NG). In patients with a STN, a hypoactive nodule with a high TUS has a higher probability of malignancy; whereas a hyperactive nodule with a high TUS is a follicular adenoma. In patients with MNG, a hypoactive nodule with a high TUS may be suggestive of malignancy despite a benign FNAC result. We think that further studies with Tc-99m-TF are required to confirm these results.

Use of liposomes as carriers for radiation synovectomy.

Using [99mTc]pertechnetate as an aqueous space marker, the permeability of liposomes composed of seven different mixtures of distearoylphosphatidylcholine (DSPC) and sphingomyelin (SM) was determined. Liposomes containing 20-33% SM were the least permeable in the presence of rheumatoid synovial fluid. Following injection of 99mTc-containing liposomes into the knee joints of rabbits, retention of 99mTc in the knee was more than 200 times greater than following injection of nonencapsulated [99mTc]pertechnetate. The knee clearance biologic half time of 99mTc with DSPC/SM (4:1) liposomes was 64 h. Most of the activity that had leaked from the knee was not found in extra-articular tissues, suggesting rapid excretion. When DSPC/SM (4:1) liposomes were labeled with 111In(oxine), a knee clearance biologic half time of greater than 1200 h was observed.