K. Solanki

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.

Clinical evaluation of technetium-99m infecton for the localisation of bacterial infection.

The aim of the study was to distinguish infection from inflammation in patients with suspected infection using technetium-99m Infecton. Ninety-nine patients (102 studies) referred for infection evaluation underwent imaging with 400 MBq99mTc-Infecton at 1 and 4 h. Most patients had appropriate microbiological tests and about half (56) had radiolabelled white cell scans as well. No adverse effects were noted in any patient. The clinical efficacy of99mTc-Infecton depended in part on whether imaging was undertaken during intibiotic therapy for infection or not. In consultation with the microbiologist, 5–14 days of appropriate and successful antibiotic therapy was considered adequate to classify some results as true-negatives. The figures for sensitivity and specificity of99mTc-Infecton for active or unsuccessfully treated infection were 83% and 91% respectively. It is concluded that99mTc-Infecton imaging contributed to the differential diagnosis of inflammation. It is being used as the first imaging modality when bacterial infection is suspected.

Imaging bacterial infection with 99mTc-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.

Clinical experience with 99mTc-MAG3, mercaptoacetyltriglycine, and a comparison with 99mTc-DTPA

The preparation, application and clinical usage of 99mTc-mercaptoacetyltriglycine, MAG3, a tubular secreted compound, is described in the first 225 patients in a phase III study. Image quality, relative renal function, and renal transit times were compared with a 4 fold greater administered activity of 99mTc-DTPA in 11 patients. Correlation coefficients of 0.94 for relative function, 0.83 for parenchymal transit time index and 0.82 for whole kidney transit time index were found. Frusemide responses were similar. 99mTc-MAG3 is an efficacious radiopharmaceutical for routine renal radionuclide studies, giving excellent image quality in patients with hypertension, poor renal function, obstructive nephropathy or a renal transplant.

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.

99Tcm-labelled leucocyte imaging in active rheumatoid arthritis

A simplified technique of labelling leucocytes with technetium-99m is described and applied to patients with active rheumatoid arthritis. The clinically active and less active knees in seven patients were imaged and the uptake of labelled leucocytes was measured. The measurements were repeated after local steroid injection into nine painful knees. A 50-80% reduction in leucocyte uptake localized to the region of the synovium was demonstrated in the eight knees which showed clinical responses and a rise of 8% in the non-responder. There was a variable response in the knees that were not injected. 99Tcm leucocyte imaging in rheumatoid arthritis is able to assess objectively joint inflammation and its response to treatment.

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.

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.

Cerebral uptake of MIBG: adrenoceptors visualized?

Radiolabelled metaiodobenzylguanidine (MIBG) localizes in adrenergic neurones. A study was carried out to evaluate the uptake of this radiopharmaceutical in cerebral tissues. Twenty-three patients with neural crest tumours, who had no evidence of central nervous system disease, were evaluated. Each patient underwent a diagnostic MIBG study, followed by a therapy dose with 131I-MIBG and subsequent scintigraphy. Focal uptake was seen in the cerebellum (CB), basal nuclei and thalamic region (BNTr), 24 and 48 h postinjection on the diagnostic images. The BNTr to cerebral cortex ratio ranged from 1.05 to 1.79. Uptake was also seen on the days 2, 3, 4 and 6 post-therapy images. Single photon emission computed tomography (SPECT) clearly outlined the uptake in the CB and BNTr. The BNTr to cerebral cortex ratio ranged from 1.10 to 1.85 and CB to cerebral cortex ratio from 1.18 to 2.01. It is hypothesized that the focal uptake observed in the CB and BNTr is due to adrenergic receptor binding. It is felt that SPECT with radiolabelled MIBG may prove to be a useful tracer for mapping the adrenergic receptors in the human brain.