Flushing and subsequent retrograde filling of the bladder results in the highest rate of tumour visualization and quantification. Flushing alone is inferior.
Rat genotypes differ in their susceptibility to spontaneously occurring spike-wave discharges and in their dopaminergic properties. In a previous study, it was found that spike-wave discharge incidence decreased in the following order in four rat genotypes during baseline and following injection with the dopamine antagonist haloperidol: apomorphine-susceptible (APO-SUS) > WAG/Rij > apomorphine-unsusceptible (APO-UNSUS) and ACI rats. The question in the present study was to what extent certain dopaminergic properties are pathognomonic for epileptic rats. Therefore, behavioral responses were assessed in order to investigate the dopaminergic properties in the four rat genotypes. Apomorphine-induced gnawing data imply that the dopamine activity of the nigrostriatal system in the WAG/Rij rats is higher than in APO-SUS but lower than in the ACI and APO-UNSUS rats. Furthermore, in previous studies APO-SUS have been shown to have a higher novelty/amphetamine-induced locomotion, indicative of a higher dopamine reactivity of the mesolimbic system as compared to APO-UNSUS rats. Results from the present study showed that WAG/Rij rats have a higher locomotor responsiveness to novelty/amphetamine, indicating a higher dopamine reactivity of the mesolimbic system in comparison to the ACI rats. It is suggested that the functional dopaminergic mesolimbic dominance is an important factor in the susceptibility to show spontaneously occurring spike-wave discharges.
Rationale
Salivary glands are highly perfused and express the prostate-specific membrane antigen (PSMA) receptor as well as the sodium—iodide symporter. As a consequence, treatment with 177Lu/225Ac-PSMA for prostate cancer or 131I for thyroid cancer leads to a high radiation dose in the salivary glands, and patients can be confronted with persistent xerostomia and reduced quality of life. Salivation can be inhibited using an antimuscarinic pharmaceutical, such as glycopyrronium bromide (GPB), which may also reduce perfusion. The primary objective of this work was to determine if inhibition with GPB could provide a considerable (> 30%) reduction in the accumulation of administered 123I or 68Ga-PSMA-11 in salivary glands.
Methods
Ten patients who already received a whole-body 68Ga-PSMA-11 PET/CT scan for (re)staging of prostate cancer underwent a repeat PET/CT scan with tracer administration at 90 min after intravenous injection of 0.2 mg GPB. Four patients in follow-up after thyroid cancer, who had been treated with one round of ablative 131I therapy with curative intent and had no signs of recurrence, received 123I planar scintigraphy at 4 h after tracer administration without GPB and a repeated scan at least one week later, with tracer administration at 30 min after intramuscular injection of 0.4 mg GPB. Tracer uptake in the salivary glands was quantified on PET and scintigraphy, respectively, and values with and without GPB were compared.
Results
No significant difference in PSMA uptake in the salivary glands was seen without or with GPB (Mean SULmean parotid glands control 5.57, intervention 5.72, p = 0.50. Mean SULmean submandibular glands control 6.25, intervention 5.89, p = 0.12). Three out of 4 patients showed increased 123I uptake in the salivary glands after GPB (Mean counts per pixel control 8.60, intervention 11.46).
Conclusion
Muscarinic inhibition of salivation with GPB did not significantly reduce the uptake of PSMA-ligands or radioiodine in salivary glands, and can be dismissed as a potential strategy to reduce toxicity from radionuclide therapies.
Radiation therapy is an effective treatment modality for a variety of cancers. Despite several advances in delivery techniques, its main drawback remains the deposition of dose in normal tissues which can result in toxicity. Common practices of evaluating toxicity, using questionnaires and grading systems, provide little underlying information beyond subjective scores, and this can limit further optimization of treatment strategies. Nuclear medicine imaging techniques can be utilised to directly measure regional baseline function and function loss from internal/external radiation therapy within normal tissues in an in vivo setting with high spatial resolution. This can be correlated with dose delivered by radiotherapy techniques to establish objective dose-effect relationships, and can also be used in the treatment planning step to spare normal tissues more efficiently. Toxicity in radionuclide therapy typically occurs due to undesired off-target uptake in normal tissues. Molecular imaging using diagnostic analogues of therapeutic radionuclides can be used to test various interventional protective strategies that can potentially reduce this normal tissue uptake without compromising tumour uptake. We provide an overview of the existing literature on these applications of nuclear medicine imaging in diverse normal tissue types utilising various tracers, and discuss its future potential.
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