Fasting Enhances the Contrast of Bone Metastatic Lesions in 18F-Fluciclovine-PET: Preclinical Study Using a Rat Model of Mixed Osteolytic/Osteoblastic Bone Metastases.

18F-fluciclovine (trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid) is an amino acid positron emission tomography (PET) tracer used for cancer staging (e.g., prostate and breast). Patients scheduled to undergo amino acid-PET are usually required to fast before PET tracer administration. However, there have been no reports addressing whether fasting improves fluciclovine-PET imaging. In this study, the authors investigated the influence of fasting on fluciclovine-PET using triple-tracer autoradiography with 14C-fluciclovine, [5,6-³H]-2-fluoro-2-deoxy-d-glucose (³H-FDG), and 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) in a rat breast cancer model of mixed osteolytic/osteoblastic bone metastases in which the animals fasted overnight. Lesion accumulation of each tracer was evaluated using the target-to-background (muscle) ratio. The mean ratios of 14C-fluciclovine in osteolytic lesions were 4.6 ± 0.8 and 2.8 ± 0.6, respectively, with and without fasting, while those for ³H-FDG were 6.9 ± 2.5 and 5.1 ± 2.0, respectively. In the peri-tumor bone formation regions (osteoblastic), where 99mTc-HMDP accumulated, the ratios of 14C-fluciclovine were 4.3 ± 1.4 and 2.4 ± 0.7, respectively, and those of ³H-FDG were 6.2 ± 3.8 and 3.3 ± 2.2, respectively, with and without fasting. These results suggest that fasting before 18F-fluciclovine-PET improves the contrast between osteolytic and osteoblastic bone metastatic lesions and background, as well as 18F-FDG-PET.

Contamination, a Major Problem in Nuclear Medicine Imaging: How to Investigate, Handle, and Avoid It.

We present a case study in which artifacts from collimator contamination and patient motion were seen on a bone scan. Any identified artifact must be further investigated and documented so as to detect its source and thus prevent its future occurrence.

Miniaturized Radiochemical Purity Testing for 99mTc-HMPAO, 99mTc-HMDP, and 99mTc-Tetrofosmin.

Quick methods are functional in clinical practice to ensure the fastest availability of radiopharmaceuticals. For this purpose, we investigated the radiochemical purity of the widely used 99mTc-hydroxymethylene diphosphonate, 99mTc-hexamethylpropyleneamine oxime, and 99mTc-tetrofosmin by reducing time as compared with the manufacturer's method. Methods: We applied a miniaturized chromatographic method with a reduced strip development from 18 cm to 9 cm for all 3 radiopharmaceuticals. The specific support medium and solvent system of the manufacturer's methods was kept unchanged for 99mTc-hydroxymethylene diphosphonate and 99mTc-tetrofosmin, whereas for 99mTc-hexamethylpropyleneamine oxime the instant thin-layer chromatography (ITLC) polysilicic gel (silicic acid [SA]) was replaced with a monosilicic gel (silicic gel [SG]) in the chromatographic system that uses methyl ethyl ketone as solvent. The method was applied and compared with the routine ITLC insert method in a total of 30 batches for each radiopharmaceutical. The precision of repeated tests was determined by comparison with the results of 10 replications on the same batch. Small volumes of concentrated 99mTcO4-, and 99mTc-albumin nanocolloid were used to produce potential radiochemical impurities. Correlation between the quick methods and the insert methods was analyzed using a nonparametric 2-tailed test and a 2 × 2 contingency table with the associated Fisher exact test to evaluate sensitivity and specificity. A receiver-operating-characteristic analysis was performed to evaluate the best cutoff. Results: The percentage radiochemical purity of the quick methods agreed with the standard chromatography procedures. We found that 99mTcO4 and colloidal impurities are not the only common radiochemical impurities with 99mTc-tetrofosmin, and shortening of the ITLC strip with respect to the manufacturer's method will worsen system resolution and may produce inaccuracy. Conclusion: The miniaturized methods we described represent a fast and reliable alternative for 99mTc-exametazime and 99mTc-oxidronate quality control, with the upper cutoff for acceptable radiochemical purity values being 84% and 95%, respectively. For 99mTc-tetrofosmin radiochemical purity testing, a longer strip as described in the standard method is warranted.

Detection of bone metastases in breast cancer patients in the PET/CT era: Do we still need the bone scan?

AIM: To examine the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for the detection of bone metastasis in breast cancer patients and assess whether whole body bone scan (BS) with (99m)Tc-methylene diphosphonate provides any additional information. MATERIAL AND METHODS: Study group comprised 150 patients, mean age 52 years (range 27-85) with breast cancer, suspected of having bone metastases. All patients had undergone both FDG-PET/CT and BS with or without single photon emission tomography/computed tomography (SPECT/CT) within a period of 6 weeks. The final diagnosis of bone metastasis was established by histopathological findings, additional imaging, or clinical follow-up longer than 10 months. Cancer antigen 15-3 (CA15-3) and carcinoembryogenic antigen (CEA) were measured in all patients. RESULTS: Histologically 83%, 7% and 10% had infiltrating ductal, lobular and mixed carcinoma respectively. Confirmed bone metastases were present in 86 patients (57.3%) and absent in 64 (42.7%). Mean CA15-3 and CEA values in patients with bone metastases were 74.6ng/mL and 60.4U/mL respectively, compared to 21.3ng/mL and 3.2U/mL without metastases (p<0.001). The sensitivity of FDG-PET/CT for the detection of bone metastases was 97.6% compared to 89.5% with SPECT/CT. In 57 patients, FDG-PET/CT correctly identified additional pulmonary, hepatic, nodal and other soft tissue metastases, not detected by BS. CONCLUSION: Our findings suggest that FDG-PET/CT is superior to BS with or without SPECT/CT.

Numb chin syndrome as a manifestation of jaw metastasis diagnosed in a bone scan.

In many cases, numb chin syndrome (NCS) may represent a banal pathology. However, as it can be associated with malignant processes, its presence should alert the clinician of a possible occult disease. In patients already diagnosed with cancer, it often represents an ominous sign that indicates poor prognosis, due to the rapid progress of the disease. The case is presented of a 62-year-old man diagnosed with synchronous lung and bladder cancer, who suddenly complained of numbness in the chin. The bone scan confirmed the suspicion of metastastic bone disease, and the patient died two months after the appearance of this sign.

Wipe tests to assess 99Tcm surface contamination: effects of surface type, swab type and chemical form.

The efficacy of wipe tests for assessing 99Tcm surface contamination was measured. Four types of surface were contaminated with four radiopharmaceuticals and wiped using four types of swab. The fraction of activity removed was measured by direct monitoring for each combination of surface, pharmaceutical and swab. The results obtained showed that wipe tests are neither accurate nor precise. Observed wipe efficacies differed greatly from the customary assumption that 10% of the activity is removed by wiping. Detergent soaked swabs gave a mean efficacy of 40%, although with considerable variation (coefficient of variation 49%). Using these swabs alone the surface type affected efficacy by almost a factor three (floor tile mean efficacy 20%, plastic laminate mean efficacy 57%). In principle this effect might be compensated for by using correction factors according to the surface being swabbed. However, the pharmaceutical type will generally be unknown, and this also affected efficacy by almost a factor of two (eluate mean efficacy 29%, macroaggregated albumin 53%). Overall the results suggest that wipe tests can be used to detect contamination but are unreliable for quantification.

Radiation hazards from horses undergoing scintigraphy using technetium-99m.

This paper quantifies the extent of the radiation hazard to personnel from horses undergoing scintigraphy using technetium99m methylene diphosphonate (99Tcm-MDP). From the data produced it is possible to derive safe working protocols which are comfortably within the legislated limits for whole body doses as set out in the Ionising Radiations Regulations 1985. Measurements were made of the surface and environmental activities which result from individuals undergoing scintigraphic evaluation and also from urine contaminated bedding. The use of both high and low activities in the assessment of the radiation hazard to personnel and owners is considered.

Paper chromatographic and paper elettrophoretic study of the solution chemistry of Tc-99m-methylendiphosphonate and of Tc-99m-dimercaptosuccinate for improving the tumour-affinity of Tc-99m during scintigraphic imaging of cancer.

In order to find the conditions under which Tc-99m-methylenediphosphonate (Tc-99m-MDP) and Tc-99m(V)-dimercaptosuccinate (Tc-99m(V)-DMSA) may become tumour-seeking agents, leaving healthy organs free from the radionuclide uptake, the solution chemistry of these radiopharmaceuticals was studied by paper chromatography and paper electrophoresis in distilled water, in physiological saline, in NAHCO3, and ascorbic acid solutions. Both radiopharmaceuticals are anionic in the radiopharmaceutical solution but get easily hydrolysed to form cationic Tc-99m species which concentrates in healthy bone and in some bone metastases. Tc-99m (V)-DMSA being more stable remains long in the blood pool giving undesirable presence of the radionuclide in lung, heart and kidneys, in addition to its reduced uptake in bone metastases and in some primaries. We are trying to eliminate these drawbacks of healthy organ uptake of Tc-99-m(V)-DMSA not only to get a clean scintigraphic image of the tumour with this radiopharmaceutical but to extend its formulation, thus obtained, to prepare radiopharmaceutical with Re-188, which is the higher homologue of Tc-99m, for systemic therapy of cancer. Essentially similar solution chemistry of both radiopharmaceuticals suggests that like Tc-99m-MDP, technetium-99m-dimercaptosuccinate is also a complex of tetravalent Tc-99m and not of pentavalent Tc-99m as so far supposed to be.

[Simplified analytical method of 99mTc-labeled phosphonate].

A simplified and rapid analytical method of 99mTc-labeled phosphonates was tested using a mini-column based on an anion-exchange type of cartridge. Free 99mTcO4- in the prepared solutions of 99mTc-labeled phosphonate was eluted from the column by a neutral phosphate buffer solution. Partly components of the 99mTc-labeled phosphonates was eluted from the column by a 100 mM sodium phosphonate solution, while the residual components were not eluted from the mini-column. In addition, for analysis of 99mTc-labeling rate in 99mTc-MDP solution, this method requires much less time than thin layer chromatography (TLC). Therefore, the method is more suitable for analysis of 99mTc-labeled phosphonates than TLC now in use, particularly rapid analysis for 99mTc-labeling rate of the compounds and the stability.

Multifunctional calcium phosphate nano-contrast agent for combined nuclear, magnetic and near-infrared in vivo imaging.

Combination of three imaging techniques such as nuclear, magnetic and near-infrared fluorescence can aid in improved diagnosis of disease by synergizing specific advantages of each of these techniques such as deep tissue penetration of radiation signals, anatomical and functional details provided by magnetic contrast and better spatial resolution of optical signals. In the present work, we report the development of a multimodal contrast agent based on calcium phosphate nanoparticles (nCP), doped with both indocyanine green (ICG) and Gadolinium (Gd(3+)), and labeled with 99m-Technetium-methylene diphosphonate ((99m)Tc-MDP) for combined optical, magnetic and nuclear imaging. In order to obtain the desired tri-modal contrast properties, the concentrations of ICG, Gd(3+) and (99m)Tc were optimized at ∼0.15wt%, 3.38at% and ∼0.002ng/mg of nCP, respectively. The leaching-out of ICG was protected by an additional coating of polyethyleneimine (PEI). Toxicological evaluation of the final construct carried out on healthy human mononuclear cells, red-blood cells and platelets, showed excellent hemocompatibility. In vivo multimodal imaging using mice models revealed the ability to provide near-infrared, magnetic and nuclear contrast simultaneously. The nanoparticles also showed the potential for improved MR based angio-imaging of liver. Retention of intravenously administrated nanoparticles in the liver was reduced with PEGylation and the clearance was observed within 48h without causing any major histological changes in vital organs. Thus, we developed a non-toxic tri-modal nano-contrast agent using calcium phosphate nanoparticles and demonstrated its potential for combined nuclear, magnetic and near-infrared imaging in vivo.

Quantitative HPLC determination of [99mTc]-pertechnetate in radiopharmaceuticals and biological samples--I. Technique development.

Techniques have been developed which allow HPLC (high performance liquid chromatography) to be used for the quantitative determination of [99mTc]pertechnetate in radiopharmaceuticals and biological samples. An instrumental technique accounts for 99mTc species which do not elute from the HPLC column, while a chemical technique obviates interferences caused by Sn(II). These two techniques are incorporated into an anion exchange HPLC procedure which is applied to the determination of [99mTc]pertechnetate in 99mTc-diphosphonate radiopharmaceuticals and biological samples.

Indirect spectrophotometric determination of BIDA, DISIDA, DTPA and MDP in labelled compounds.

N-(4-(n-butyl)-acetanilide)iminodiacetic acid (BIDA), N-(2,6-diisopropylacetanilide)iminodiacetic acid (DISIDA), diethylenetriaminepentaacetic acid (DTPA) and methylene diphosphonic acid (MDP) are used in labelling kits. The contents of BIDA, DISIDA or MDP of the 99mTc-labelled compounds can be determined (indirectly) spectrophotometrically with copper, eriochrome cyaanine R (ECC) and dodecylethyldimethylammonium bromide (DEDA) in a sodium barbital buffered system at pH 8.5. The calibration curves obey Beer's Law from 0 to 40 micrograms/25 mL for BIDA and DISIDA, 0 to 60 micrograms/25 mL for DTPA and 0 to 100 micrograms/10 mL for MDP.

Bone changes due to hyperbaric exposure.

Based on the hypothesis that bone calcification is promoted by loading physical pressure, changes in the microstructure of the bone under hyperbaric conditions were analyzed by imaging technology. Hyperbaric exposure was carried out for two weeks at 2 atm (equal to the pressure at a depth of water of 10 m) which was achieved using a mixed gas of helium and oxygen (He:O2 88%:12%) in which the oxygen partial pressure was maintained at constant (PO2: 0.21 bar). In image technological analysis, the growth and development of the bone were evaluated at different stages using Digital Magnification Radiography (DMR) images and based on changes in the X-ray absorption ratio. DMR images after hyperbaric exposure showed calcification in the heads of long bones (humeri, femora, and tibiae) in mice. There were also significant changes in the X-ray absorption ratio in the heads. The accumulation of 99mTc-MDP was higher in all long-bone heads after hyperbaric exposure than before exposure. These results suggest that the hyperbaric environment promotes bone calcification.

Macrophage targeting with 99mTc-labelled J001 for scintigraphic assessment of experimental osteoarthritis in the rabbit.

The potential of scintigraphy with technetium 99m-labelled J001 (99mTc-J001) to detect synovitis was studied in 15 rabbits with osteoarthritis (OA) of the right knee (section of cruciate ligaments), in five sham-operated rabbits and in four non-operated rabbits. J001 is a non-pyrogenic, acylated poly (1,3) galactoside isolated from the membrane of a non-pathogenic strain of Klebsiella pneumoniae which is able to bind selectively to macrophages via the binding to CD11b and CD14 molecules. The results of 99mTc-J001 scintigraphy were compared with those of scintigraphy with 99mTc-labelled methylene diphosphonate (99mTc-MDP) and GC-APG (a derivative of J001 unable to bind macrophages in vitro). The mean scintigraphic ratios (diseased healthy knee) of 99mTc-J001 were significantly higher in OA rabbits than in sham- and non-operated rabbits, from as early as day 18 until day 90. 99mTc-J001 scintigraphy demonstrated earlier increased uptake than 99mTc-MDP scintigraphy. The mean scintigraphic ratios of 99mTc-J001 were significantly higher than those of 99mTc-GC-APG (which remained normal) in OA rabbits. The normal scintigraphic ratios of 99mTc-J001 in sham-operated and non-operated rabbits, as well as of 99mTc-GC-APG in OA rabbits, suggested that the increased uptake demonstrated with 99mTc-J001 in OA rabbits, as early as day 18 corresponded to imaging of synovitis via elective macrophage targeting. These results showed that 99mTc-J001 scintigraphy should be a specific method of detecting synovitis in OA.

Deposiçäo testicular de 99m Tc-MDP / 99m Tc-MDP deposition in the testis

Os autores apresentam um caso de deposiçäo de 99m Tc-MDP em testículos de paciente que havia sido submetido a orquiectomia terapêutica por adenocarcinoma de próstata há seis anos passados. Procedem breve revisäo da literatura e assinalam os mecanismos aventados para justificar o evento