Enhanced antiopiate activity and enzyme resistance in peptidomimetics of FMRFamide containing (E)-2,3-methanomethionine.

FMRFamide is a molluscan peptide that has shown antiopiate activity in a number of mammalian test systems. The current study determined the antiopiate potency of FMRFamide and two conformationally constrained peptidomimetics of FMRFamide containing stereoisomers of (E)-2,3-methanomethionine. Morphine abstinence signs were observed after varying doses (0.25-25.0 microgram) of these substances were injected into the third ventricle of morphine-dependent rats. Both peptidomimetics were far more potent than FMRFamide itself. In addition, although both peptidomimetics bound with lower affinity than FMRFamide to rat spinal cord receptors for NPFF (the mammalian FMRFamide-like peptide), they were far more resistant than FMRFamide to enzymatic degradation by leucine aminopeptidase.

Differentiated thyroid cancer: lobectomy and radioiodine, a treatment suitable for all cases?

When treating differentiated carcinoma of the thyroid, lobectomy is the minimum surgical requirement, but there is a strong case for ablation of the whole gland. Controversy centres on the management of the contralateral lobe, which may be ablated by total thyroidectomy, by near total thyroidectomy and ablation of thyroid fragments by 131I, or by 131I alone. Operative morbidity is increased after total thyroidectomy compared with lobectomy. However, radioactive 131I ablation of the contralateral lobe is associated with a longer period of hospitalization than if radioactive 131I is given to ablate residual fragments of thyroid tissue after total thyroidectomy. The use of lobectomy may lead to a higher incidence of patients requiring more than one administration of 131I. The evidence available indicates that radioactive 131I ablation of the contralateral lobe is a safe procedure unless tumour deposits within this lobe are large enough to be visualized on an ultrasound scan, when total thyroidectomy becomes mandatory. Clinical trials are necessary to test this hypothesis.

An assessment of finger doses received by staff while preparing and injecting radiopharmaceuticals.

Good working practice and legal obligation impose a duty on nuclear medicine departments to check syringe activities before administration to a patient. If syringe guards are used to reduce staff exposure while drawing up injections, the guard has to be removed to measure the activity in a conventional reentrant ionization chamber type calibrator. Alternatively, the activity may be checked in a purpose-built syringe calibrator which allows the assay of the activity in the syringe without the need to remove the syringe guard. Finger doses received during the dose preparation and injection are a cause for concern. This study investigated the finger and whole-body doses received when using each of these calibrators, and compared the results with those obtained by an operator who did not measure the dose at all. The results demonstrated that although the finger doses are small, measurement of the syringe activities in a conventional ionization chamber increases the dose by a factor of 2 above that which would occur if no activity measurements were made, whereas the use of the specialized syringe calibrator gave finger doses only marginally above those obtained with no activity measurement.

The diagnostic value of positron emission tomography (PET) with radiolabelled fluorodeoxyglucose (18F-FDG) in head and neck cancer.

Positron emission tomography (PET) scanning has recently been introduced into clinical practice but its usefulness in the management of head and neck cancer is not well defined. The aim of this prospective preliminary study was to examine the clinical value of fluorodeoxyglucose (FDG)--PET in patients with head and neck cancer treated by radiotherapy with surgery in reserve by (i) relating quantitative uptake of isotope to tumour type and histological grade and (ii) comparing the imaging findings of PET and magnetic resonance imaging (MRI) in post-radiotherapy assessment of tumour response. Twenty-one patients had pre-treatment PET and MRI scans and these were repeated four and eight months after treatment if there was no clinical relapse. Pre-treatment uptake of FDG using tumour to cerebellar ratio parameters was significantly related to the histological grade of squamous cancer (p = 0.04) but not to tumour type. Discordance of post-treatment PET/MRI findings in one case indicates a possible role for PET in the early detection of tumour recurrence. Other potential uses of PET scanning in the management of head and neck cancer are discussed.

Edited 31P brain spectra using maximum entropy data processing.

Strategies for estimating peak areas in 31P brain spectra are discussed, and the widespread convolution difference method is analyzed. The Skilling maximum entropy method (MEM) algorithm is applied to in vivo spectra and provides an estimate of the spectrum that is operator-independent, although at the expense of some negative bias. It may be possible to overcome this bias.

Feasibility of imaging photodynamic injury to tumours by high-resolution positron emission tomography.

One early effect of the treatment of tumours by the new modality photodynamic therapy (PDT) is a reduction in tumour glucose levels. We have employed the widely used positron-emitting glucose analogue flurorine-18 fluoro-2-deoxy-D-glucose ([18F]-FDG), to determine whether, in principle, PDT-induced injury might be delineated non-invasively and quantitatively by positron emission tomography (PET). The scanner was of the high-density avalanche-chamber (HIDAC) type with a resolution of 2.6 mm. Subcutaneous T50/80 mouse mammary tumours, sensitised by haematoporphyrin ester, were illuminated by graded doses of interstitial 630 nm light. Thirty hours later, any remaining viable tumour was detected (a) by region-of-interest analysis of the PET images and (b) by gamma counting the excised tumour. PET measurements of % uptake of [18F]-FDG into tumour correlated closely with ex vivo gamma counting (slope=0.976, r2=0. 995), validating the in situ method. Uptake into untreated, control tumours was 3.8%+/-1.1% of the injected activity. Uptake of [18F]-FDG into treated tumours decreased by 0.7% for every 100 mm3 reduction in remaining viable histological volume. Outcome was further compared with that measured by (a) T2-weighted proton imaging on a 4.7-T magnetic resonance imaging (MRI) system and (b) histological analysis of subsequently sectioned tumours. PET using [18F]-FDG described the absolute volume of surviving tumour histological mass to the same degree as high-resolution MRI. The conclusion of these initial studies is that PET with [18F]-FDG, although non-specific, quantitatively described at early times the extent of tumour destruction by PDT.

Positron emission tomography of murine liver metastases and the effects of treatment by combretastatin A-4.

There are major potential advantages in non-invasive measurement of preclinical tumour biology and therapeutic response in clinically relevant, internal body sites, notably the ability to follow outcome in individual animals rather than averaging results from groups. We have exploited positron emission tomography (PET) to determine the feasibility of detecting liver metastases in B6D2F1 mice using fluorine-18 fluorodeoxyglucose ([18F]FDG) both before and after treatment by the novel cytotoxic agent, combretastatin A-4. The normal distribution of [18F]FDG in the absence of disease was characterised, with the clear delineation of the brain, the heart and the urinary bladder in all studies. In untreated mice with liver metastases, a strong correlation (r2 = 0.98) was found between the quantitative estimates of [18F]FDG uptake obtained by analysis of PET images, and those obtained from ex vivo assay of liver plus metastases excised immediately after imaging. In this first series, the effective limit of resolution was in livers containing a number of small metastases (range 8-14) with a single volume equivalent of approximately 200 mm3. PET image analysis was concordant with histological measurements in showing that single intraperitoneal doses of combretastatin A-4 resulted in an average 30% volume destruction of metastatic mass by 24 h following administration.