Predictive and prognostic potential of pretreatment 68Ga-PSMA PET tumor heterogeneity index in patients with metastatic castration-resistant prostate cancer treated with 177Lu-PSMA.

Introduction: This study was conducted to evaluate the predictive values of volumetric parameters and radiomic features (RFs) extracted from pretreatment 68Ga-PSMA PET and baseline clinical parameters in response to 177Lu-PSMA therapy. Materials and methods: In this retrospective multicenter study, mCRPC patients undergoing 177Lu-PSMA therapy were enrolled. According to the outcome of therapy, the patients were classified into two groups including positive biochemical response (BCR) (≥ 50% reduction in the serum PSA value) and negative BCR (< 50%). Sixty-five RFs, eight volumetric parameters, and also seventeen clinical parameters were evaluated for the prediction of BCR. In addition, the impact of such parameters on overall survival (OS) was evaluated. Results: 33 prostate cancer patients with a median age of 69 years (range: 49-89) were enrolled. BCR was observed in 22 cases (66%), and 16 cases (48.5%) died during the follow-up time. The results of Spearman correlation test indicated a significant relationship between BCR and treatment cycle, administered dose, HISTO energy, GLCM entropy, and GLZLM LZLGE (p<0.05). In addition, according to the Mann-Whitney U test, age, cycle, dose, GLCM entropy, and GLZLM LZLGE were significantly different between BCR and non BCR patients (p<0.05). According to the ROC curve analysis for feature selection for prediction of BCR, GLCM entropy, age, treatment cycle, and administered dose showed acceptable results (p<0.05). According to SVM for assessing the best model for prediction of response to therapy, GLCM entropy alone showed the highest predictive performance in treatment planning. For the entire cohort, the Kaplan-Meier test revealed a median OS of 21 months (95% CI: 12.12-29.88). The median OS was estimated at 26 months (95% CI: 17.43-34.56) for BCR patients and 13 months (95% CI: 9.18-16.81) for non BCR patients. Among all variables included in the Kaplan Meier, the only response to therapy was statistically significant (p=0.01). Conclusion: This exploratory study showed that the heterogeneity parameter of pretreatment 68Ga-PSMA PET images might be a potential predictive value for response to 177Lu-PSMA therapy in mCRPC; however, further prospective studies need to be carried out to verify these findings.

ImmunoPET: Antibody-Based PET Imaging in Solid Tumors.

Immuno-positron emission tomography (immunoPET) is a molecular imaging modality combining the high sensitivity of PET with the specific targeting ability of monoclonal antibodies. Various radioimmunotracers have been successfully developed to target a broad spectrum of molecules expressed by malignant cells or tumor microenvironments. Only a few are translated into clinical studies and barely into clinical practices. Some drawbacks include slow radioimmunotracer kinetics, high physiologic uptake in lymphoid organs, and heterogeneous activity in tumoral lesions. Measures are taken to overcome the disadvantages, and new tracers are being developed. In this review, we aim to mention the fundamental components of immunoPET imaging, explore the groundbreaking success achieved using this new technique, and review different radioimmunotracers employed in various solid tumors to elaborate on this relatively new imaging modality.

Sub dissociative dose of ketamine with haloperidol versus fentanyl on pain reduction in patients with acute pain in the emergency department; a randomized clinical trial.

BACKGROUND: Ketamine is known to be an effective factor in reducing pain without significant side effects. OBJECTIVE: One of the limited side effects of Ketamine is agitation. Due to the reduction of this symptom with Haloperidol, we decided to design a randomized clinical trial to compare the analgesic effect of Ketamine with Haloperidol and Fentanyl in reducing acute pain and its complications. METHODS: In this study, 200 adult patients who presented to the emergency department with acute pain are examined. They are randomly divided into two groups. One group received intravenous Ketamine with Haloperidol and the other group received intravenous Fentanyl. Patients are then compared for their pain score before and after administration of the drugs, as well as the side effects they experienced. RESULTS: There was no significant difference between the mean scores of initial pain in the two groups, but at all intervals of 5, 10, 15 and 30 min after injection, the mean of pain scores of patients in the group receiving Ketamine and Haloperidol were lower. The need for injection of rescue analgesic was 9% in the Ketamine and Haloperidol group and 34% in the Fentanyl group. The mean agitation score did not differ between the two groups except in the tenth minute. At tenth minute, the mean agitation score of the Ketamine group was higher. CONCLUSION: Ketamine works better than fentanyl in controlling acute pain, and limited side effect of agitation can be controlled if injected with haloperidol. Due to its better function and fewer side effects, it seems that in controlling acute pain, Ketamine along with Haloperidol can be a good alternative to opioids.

Anticonvulsive Effects of Licofelone on Status Epilepticus Induced by Lithium-pilocarpine in Wistar Rats: a Role for Inducible Nitric Oxide Synthase.

BACKGROUND AND PURPOSE: Status epilepticus (SE) is a neurological disorder with high prevalence and mortality rates, requiring immediate intervention. Licofelone is a cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibitor, which its effectiveness to treat osteoarthritis has been approved. Increasing evidence suggests an involvement of COX and LOX enzymes in epileptic disorders. Thus, in the present study we investigate possible effects of licofelone on prevention and termination of SE. We also evaluated whether the nitrergic system could participate in this effect of licofelone. METHODS: We have utilized lithium-pilocarpine model of SE in adult Wistar rats to assess the potential effect of licofelone on seizure susceptibility. Licofelone was administered 1 h before pilocarpine. To evaluate probable role of nitric oxide (NO) system, L-arginine (60 mg/kg, i.p.), as a NO precursor; L-NAME (15 mg/kg, i.p.), as a non-selective nitric oxide synthase (NOS) inhibitor; aminoguanidine (100 mg/kg, i.p.), as an inducible NOS (iNOS) inhibitor and 7-nitroindazole (60 mg/kg, i.p.), as a neuronal NOS inhibitor were injected 15 min before licofelone. Also, licofelone and diazepam 10 mg/kg were administered 30 minutes after onset of SE. RESULTS: Pre-treatment with licofelone at the dosage of 10 mg/kg, significantly prevented the onset of SE in all subjects (p < 0.001). L-arginine significantly inverted this anticonvulsant effect (p < 0.05). However, L-NAME and aminoguanidine, potentiated the anticonvulsant effect of licofelone (p < 0.05, p < 0.01). Licofelone could not terminate seizures after onset which was terminated by diazepam. CONCLUSIONS: Our findings showed that anticonvulsive effects of licofelone on SE could be mediated by iNOS. Also, we suggest that COX/5-LOX activation is possibly required in the initial stage of onset but SE recruits extra excitatory pathways with prolongation.