(99m)Tc glucarate as a potential radiopharmaceutical agent for assessment of tumor viability: from bench to the bed side.

Several radiotracers have been used for assessing cell death, whether by necrosis or apoptosis. (99m)Tc glucarate, which has initially been reported to be concentrating/accumulating in myocardial infarction or zones of cerebral injury, has also shown some tumor-seeking properties in a few preliminary studies. Under International Atomic Energy Agency (IAEA)'s coordinated research program, we report here the standardization, quality control, and clinical evaluation (detection, evaluation of response, and comparison with (18)F Fluorodeoxyglucose) of this tracer in well-characterized lung cancer and head neck malignancies in a single-arm prospective observational study. Forty-seven patients (29 inoperable lung carcinoma and 18 head and neck malignancies) were prospectively enrolled and underwent (99m)Tc glucarate imaging [whole body planar and single-photon emission computed tomography of the region of interest] 4-5 hours after injection of 20 mCi of the radiopharmaceutical. Excellent (99m)Tc glucarate concentration was noted in the target lesion in lung cancer and head and neck malignancies. The sensitivity was found to be better in lung cancer. Avid concentration of tracer was seen in the metastatic sites. During response evaluation, the glucarate concentration correlated well with the clinical and other radiological findings. (99m)Tc glucarate showed avid concentration of tracer in the tumor, suggesting it to be a potential tumor imaging agent which can be used for detection and assessment of therapeutic response in malignancy.

Training programmes for developing countries.

Unprecedented gains have been made in the early detection and prevention of childhood metabolic diseases. Over the last 12 years under the International Atomic Energy Agency (IAEA) Technical Cooperation Programme there have been newborn screening (NBS) projects in all the key regions--Asia, Africa, Latin America and Europe. A total of 29 projects have been undertaken at an estimated total cost of US$6.7 million, mainly focused on establishing and supporting NBS for congenital hypothyroidism. Under these projects professional training has been one of the key objectives. This short report provides a summary of the training efforts under these projects.

Imaging bacterial infection with (99m)Tc-ciprofloxacin (Infecton).

AIMS: The diagnosis of deep seated bacterial infections, such as intra-abdominal abscesses, endocarditis, and osteomyelitis, can be difficult and delayed, thereby compromising effective treatment. This study assessed the efficacy of a new radioimaging agent, Tc-99m ciprofloxacin (Infecton), in accurately detecting sites of bacterial infection. METHODS: Eight hundred and seventy nine patients with suspected bacterial infection underwent Infecton imaging and microbiological evaluation. The sensitivity and specificity of Infecton in detecting sites of bacterial infection were determined with respect to Centres of Disease Control, World Health Organisation, and Dukes's criteria. RESULTS: Five hundred and seventy four positive and 295 negative images were produced. These included 528 true positives, 46 false positives, 205 true negatives and 90 false negatives, giving an overall sensitivity of 85.4% and a specificity of 81.7% for detecting infective foci. Sensitivity was higher (87.6%) in microbiologically confirmed infections. CONCLUSIONS: Infecton is a sensitive technique, which aids in the earlier detection and treatment of a wide variety of deep seated bacterial infections. The ability to localise infective foci accurately is also important for surgical intervention, such as drainage of abscesses. In addition, serial imaging with Infecton might be useful in monitoring clinical response and optimising the duration of antimicrobial treatment.

Evaluation of the efficacy of 99mTc-Infecton, a novel agent for detecting sites of infection.

AIMS: To determine the sensitivity and specificity of 99mTc-Infecton (Infecton), a novel ciprofloxacin based imaging agent, in detecting sites of infection. METHODS: Ninety patients thought to be suffering from a variety of infections were administered 300-400 MBq of Infecton intravenously. Whole body images were taken one and four hours later. Appropriate specimens were taken for microbiological investigations. Statistical analysis was performed using a computer statistical package. RESULTS: Ninety eight Infecton images were produced. Forty one of these were positive, including three false positives, where the patients had non-infective conditions. Fifty seven negative images were obtained, of which 41 were true negatives and 16 were false negatives, having definite evidence of infection. Thus, Infecton imaging has a sensitivity of 70.3% and a specificity of 93.1% for detecting infective foci. The positive and negative predictive values were 92.6% and 71.9%, respectively. CONCLUSION: Infecton imaging is a new diagnostic tool that is specific for detecting sites of bacterial infection in the body. The high positive predictive value displayed by the technique is clinically important because a positive image strongly supports a diagnosis of bacterial infection. A negative result does not rule out an infection, and may be a result of previous or current antibiotic treatment and/or infection with organisms that do not take up Infecton. Infecton imaging has major advantages over well established imaging techniques, including radiolabelled leucocytes, and may prove to be a superior method for localising bacterial infections.

Comparison of 99mTc infecton imaging with radiolabelled white-cell imaging in the evaluation of bacterial infection.

BACKGROUND: Bacterial infection can pose a substantial diagnostic dilemma. Techniques involving radiolabelled leucocytes can pinpoint the site of inflammation. However, previous radiolabelling techniques have failed to distinguish between bacterial-mediated infection and non-bacterial inflammation. To overcome this difficulty, we have studied a radiopharmaceutical, technetium-99m (99mTc) Infecton, which is based on the antibiotic ciprofloxacin. METHODS: We used this agent to image bacterial infection in 56 patients (one twice) with known or suspected sites of infection. We then compared the imaging results of these patients with those from a radiolabelled leucocyte study. FINDINGS: The concordance rate was 68% (39 out of 57 images). In 18 discordant results 99mTc Infecton was correctly positive in 8 out of 9 positive studies and correctly negative in 4 out of 9 negative studies. 4 out of 5 of the falsely negative studies were in patients who had taken antibiotics for over 7 days. We found that 99mTc Infecton gave better imaging results than radiolabelled leucocytes. Comparison between 99mTc Infecton and leucocyte imaging gave sensitivities of 84% and 81%, and specificities of 96% and 77%, respectively. INTERPRETATION: We believe that the specificity 99mTc Infecton confers for bacterial infection and its ease of administration are the main advantages of this new agent.

Clinical evaluation of 99mTc diaminocyclohexane, a renal tubular agent with cationic transport: results in healthy human volunteers.

As alternatives to anionically transported hippuran, structure distribution experiments on a series of 99mTc-labelled primary substituted ethylene diamine compounds led to selection of 99mTc diaminocyclohexane (DACH) for clinical evaluation, 99mTc DACH, a cation with the structure trans-[O2(DACH)2 99mTc]+ is prepared by mixing 50 mumol DACH, 1 mumol stannous tartrate and 500 MBq of 99mTc. Seven normal volunteers underwent renal imaging and clearance studies using 150 MBq of 99mTc DACH and 1 MBq of 125I hippuran simultaneously. The images with 99mTc DACH revealed good uptake and excretion. The mean +/- 2 SD values of parenchymal and whole-kidney transit time indices and mean parenchymal transit time were 46 +/- 33, 75 +/- 64 and 141 +/- 51 s, respectively, similar to mercaptoacetyl triglycine. The mean clearance of 99mTc DACH was found to be 163 ml/min (SD = 32). Following cationic blockade with 900 mg oral thiamine, significant reduction (p < 0.001) in DACH clearance was noted, but hippuran clearance remained unaltered. The results support the hypothesis that 99mTc DACH is transported cationically.

The response of 99Tcm-methylene diphosphonate and 99Tcm-hexametazime-labelled neutrophils to intra-articular steroid injection in rheumatoid arthritis.

The synovial and bone uptake of tracer in the knees of patients with rheumatoid arthritis (RA) was quantified using 99Tcm-hexamethyl propylene amine oxime-labelled leucocytes and 99Tcm-methylene diphosphonate (MDP), respectively. Significant neutrophil migration and MDP uptake occurred in the knees of patients with RA irrespective of the disease duration. In all but one patient neutrophil migration was reduced after intra-articular steroid injection. The change in MDP uptake after steroid injection was variable. There was a significant correlation between the percentage reduction in neutrophil migration and pain score, while the latter correlated poorly with the change in MDP uptake. The quantification of the neutrophil component of the inflammatory process is a sensitive index for monitoring RA activity and response to pharmacological interventions, while quantitative bone scintigraphy should not be employed to monitor changes in joint inflammation in patients with RA.

A pharmacological guide to medicines which interfere with the biodistribution of radiolabelled meta-iodobenzylguanidine (MIBG).

Radiolabelled meta-iodobenzylguanidine (MIBG) is widely used in the diagnosis, follow-up and treatment of patients with tumours of neural crest origin. Some commonly prescribed and readily available over-the-counter medicines interfere with the uptake and biodistribution of this radiopharmaceutical. This may lead to poor concentration of radiolabelled MIBG within the target organs and tissues. The clinical implications are a potentially inaccurate assessment of tumour burden during diagnostic studies and a suboptimal radiation dose when MIBG is employed for targetted radiotherapy. In order to avoid false negative results a comprehensive list of prescribed and over-the-counter medicines that have the potential to inhibit uptake of MIBG has been compiled. It is hoped that this will help nuclear medicine physicians to avoid this pitfall.

A rapid method for the preparation of 99Tcm hexametazime-labelled leucocytes.

99Tcm (+/-)-hexamethylpropyleneamineoxime (HMPAO) (99Tcm Hexametazime) has been recently reported as an alternative for labelling leucocytes. For reasons of convenience, radiation dose and image quality, many workers have welcomed this novel approach except for its complicated labelling protocol and venesection of 100 ml. This technique has been modified to give a simpler routine in-house labelling technique. It has three advantages: only about 20 ml of blood is required, the labelling time is just under 1 h and high yields of labelled leucocytes are obtained (mean of 500 MBq per injection dose). The properties of labelled leucocytes using this modified method are; 80% granulocyte-bound radioactivity, a rapid lung transit and a blood granulocyte recovery of 40% at 30 min similar to those described previously. The viability of the labelled leucocytes was tested and confirmed in vitro using a migration technique and in vivo by showing no lung retention on early imaging and high splenic uptake. A rapid in-process chromatography assessment procedure for regulating the protocol has been developed. Successful abscess imaging by 4 h has been achieved in 21 patients with normal results in another 22 patients without abscesses. This simpler method should encourage a more widespread application of scintigraphy using radiolabelled granulocytes.