Intra-arterial Research Articles

EXTH-25. OPTIMIZATION OF NEW CHEMOTHERAPEUTIC AGENTS BY INTRA-ARTERIAL INFUSION IN GLIOBLASTOMAS

Abstract Being the most aggressive malignant primary brain tumor, glioblastoma (GBM) is a difficult disease to treat. The first line treatment is well established, but most patients will relapse before or during the treatments. The overall survival is only 14,6 months while the progression-free survival is 6,9 months. In Sherbrooke, Dr Fortin prioritize the intra-arterial (IA) administration of chemotherapeutic agents (CTA) as a second line treatment. Unfortunately, certain patients will not respond or will even develop chemoresistance to the agents. Therefore, there is a strong need for bringing more CTAs onto clinical care. The maximal tolerable dosage (MTD) of every agent was first determined. Every CTAs were then administered IA by retrograde infusion in the external carotid but also intravenously (IV) by the caudal vein. We used the Fischer-F98 glioma rat model in our studies. For the efficacy study, we implanted 10 000 F98 cells into their brain. After 10 days, they received the treatment associated to their group. The animals were followed every day and were euthanized when their condition was too deteriorated. The dosages found in the MTD study for topotecan and cytarabine was 4 mg/kg and 8,75 mg/kg respectively while paclitaxel was too toxic. As for the efficacy study, the IA group of topotecan showed a promising outcome with a higher survival rate (29 days) compared to the IV one (23,5 days). As for the cytarabine, the opposite was observed (IA: 22 days, IV: 26,5 days). While topotecan and cytarabine could be given intra-arterially, only topotecan showed conclusive results. More animals will be added to this group to confirm this outcome. Cytarabine is not a good option since the IV group survived a longer time than the IA group. As for the paclitaxel, the intra-tumoral infusion will be tested to see if we can get positive results.

Intra-arterial tenecteplase after successful endovascular therapy (ANGEL-TNK): protocol of a multicentre, open-label, blinded end-point, prospective, randomised trial

BackgroundDespite successful reperfusion after thrombectomy for large vessel occlusion (LVO) stroke, up to half of patients are dependent or dead at 3-month follow-up.The aim of the current study is to...

SIRT-1/RHOT-1/PGC-1α loop modulates mitochondrial biogenesis and transfer to offer resilience following endovascular stem cell therapy in ischemic stroke

Current clinical interventions for stroke majorly involve thrombolysis or thrombectomy, however, cessation of the progressive deleterious cellular cascades post-stroke and long-term neuroprotection are yet to be explored. Mitochondria are highly vulnerable organelles and their dysfunction is one of the detrimental consequences following stroke. Mitochondria dysregulation activate unfavourable cellular events over a period of time that leads to the collapse of neuronal machinery in the brain. Hence, strategies to protect and replenish mitochondria in injured neurons may be useful and needs to be explored. Stem cell therapy in ischemic stroke holds a great promise. Past studies have shown beneficial outcomes of endovascularly delivered stem cells in both pre-clinical and clinical settings. Intra-arterial (IA) administration can provide more cells to the stroke foci and affected brain regions than intravenous administration. Supplying new mitochondria to the stroke-compromised neurons either in the core or penumbra by infused stem cells can help increase their survival and longevity. Previously, our lab has demonstrated that IA 1∗105 mesenchymal stem cells (MSCs) in rats were safe, efficacious and rendered neuroprotection by regulating neuronal calcineurin, modulating sirtuin1(SIRT-1) mediated inflammasome signaling, ameliorating endoplasmic reticulum-stress, alleviation of post-stroke edema and reducing cellular apoptosis. To explore further, our present study aims to investigate the potential of IA MSCs in protecting and replenishing mitochondria in the injured neurons post-stroke and the involvement of SIRT-1/RHOT-1/PGC-1α loop towards mitochondria transfer, biogenesis, and neuroprotection. This study will open new avenues for using stem cells for ischemic stroke in clinics as one of the future adjunctive therapies.

Comparison of combined intravenous and intra-arterial thrombolysis with intravenous thrombolysis alone in stroke patients undergoing mechanical thrombectomy: a propensity-matched analysis

BackgroundA combination of intravenous (IVT) or intra-arterial (IAT) thrombolysis with mechanical thrombectomy (MT) for acute ischemic stroke due to large vessel occlusion (AIS-LVO) has been investigated. However, there is limited...

Efficacy of intra-arterial carboplatin and bevacizumab in the C6 rat glioma model of glioblastoma multiforme

BackgroundUtilizing an endovascular rat glioma model, this study aimed to analyze the efficacy of intra-arterial (IA) carboplatin and bevacizumab delivery with blood-brain barrier breakdown (BBBB) for glioblastoma treatment.MethodsC6-glioma cells were...

Impact of procedural handling on the physiological effects of alfaxalone anaesthesia in the ball python (Python regius)

To describe the cardiovascular changes following intramuscular (handled) and intravascular (undisturbed, via intraarterial catheter) alfaxalone administration, we studied 20 healthy ball pythons (Python regius) in a randomised, prospective study. The pythons were instrumented with occlusive arterial catheters to facilitate undisturbed, continuous monitoring of heart rate and blood pressure. Six pythons were administered intramuscular (IM) saline, followed by 20 mg/kg IM alfaxalone, and were manually restrained for both injections. Six pythons received intraarterial (IA) saline, followed by 10 mg/kg IA alfaxalone, and remained undisturbed for both injections. Arterial blood samples were taken at 0, 12 and 60 min post-injection, and heart rate and blood pressure were recorded for 60 min. The remaining eight snakes received 20 mg/kg IM or 10 mg/kg IA alfaxalone (n = 4 per treatment) and were not handled for intubation 10 min post-injection, to examine the effects of handling during anaesthesia. IM administration of 20 mg/kg alfaxalone or an equivalent volume of saline elicited a profound tachycardia and hypertension, which recovered to resting values after 20 min. However, when 10 mg/kg alfaxalone or saline were injected IA, mild hypotension and a lower magnitude tachycardia occurred. Arterial PCO2 and PO2, pH and lactate concentrations did not change following IA alfaxalone, but an acidosis was observed during IM alfaxalone anaesthesia. There were no significant changes in plasma catecholamines and corticosterone among treatments. Handling for injection and during anaesthesia associated with intubation significantly affects cardiovascular parameters, whereas alfaxalone per se only elicits minor changes in cardiovascular physiology.

Precision Delivery of Human Bone Marrow-Derived Mesenchymal Stem Cells Into the Pancreas Via Intra-arterial Injection Prevents the Onset of Diabetes.

Mesenchymal stem cells (MSCs) are a promising therapy to potentially treat diabetes given their potent anti-inflammatory and immune-modulatory properties. While these regenerative cells have shown considerable promise in cell culture, their clinical translation has been challenging. In part, this can be attributed to these cells not reaching the pancreas to exert their regenerative effects following conventional intravenous (IV) injection, with the majority of cells being trapped in the lungs in the pulmonary first-pass effect. In the present study, we will therefore examine whether direct delivery of MSCs to the pancreas via an intra-arterial (IA) injection can improve their therapeutic efficacy. Using a mouse model, in which repetitive low doses of STZ induced a gentle, but progressive, hyperglycemia, we tested bone marrow-derived MSCs (BM-MSCs) which we have shown are enriched with pro-angiogenic and immunomodulatory factors. In cell culture studies, BM-MSCs were shown to preserve islet viability and function following exposure to proinflammatory cytokines (IFN-γ, IL-1β, and TNF-α) through an increase in pAkt. When tested in our animal model, mice receiving IV BM-MSCs were not able to mitigate the effects of STZ, however those which received the same dose and batch of cells via IA injection were able to maintain basal and dynamic glycemic control, to similar levels as seen in healthy control animals, over 10 days. This study shows the importance of considering precision delivery approaches to ensure cell-based therapies reach their intended targets to enable them to exert their therapeutic effects.

Early therapy evaluation of intra-arterial trastuzumab injection in a human breast cancer xenograft model using multiparametric MR imaging.

To investigate the treatment efficacy of intra-arterial (IA) trastuzumab treatment using multiparametric magnetic resonance imaging (MRI) in a human breast cancer xenograft model. Human breast cancer cells (BT474) were stereotaxically injected into the brains of nude mice to obtain a xenograft model. The mice were divided into four groups and subjected to different treatments (IA treatment [IA-T], intravenous treatment [IV-T], IA saline injection [IA-S], and the sham control group). MRI was performed before and at 7 and 14 d after treatment to assess the efficacy of the treatment. The tumor volume, apparent diffusion coefficient (ADC), and dynamic contrast-enhanced (DCE) MRI parameters (Ktrans, Kep, Ve, and Vp) were measured. Tumor volumes in the IA-T group at 14 d after treatment were significantly lower than those in the IV-T group (13.1 mm3 [interquartile range 8.48-16.05] vs. 25.69 mm3 [IQR 20.39-30.29], p = 0.005), control group (IA-S, 33.83 mm3 [IQR 32.00-36.30], p<0.01), and sham control (39.71 mm3 [IQR 26.60-48.26], p <0.001). The ADC value in the IA-T group was higher than that in the control groups (IA-T, 7.62 [IQR 7.23-8.20] vs. IA-S, 6.77 [IQR 6.48-6.87], p = 0.044 and vs. sham control, 6.89 [IQR 4.93-7.48], p = 0.004). Ktrans was significantly decreased following the treatment compared to that in the control groups (p = 0.002 and p<0.001 for vs. IA-S and sham control, respectively). Tumor growth was decreased in the IV-T group compared to that in the sham control group (25.69 mm3 [IQR 20.39-30.29] vs. 39.71 mm3 [IQR 26.60-48.26], p = 0.27); there was no significant change in the MRI parameters. IA treatment with trastuzumab potentially affects the early response to treatment, including decreased tumor growth and decrease of Ktrans, in a preclinical brain tumor model.

Combination of Physicochemical Tropism and Affinity Moiety Targeting of Lipid Nanoparticles Enhances Organ Targeting.

Two camps have emerged for targeting nanoparticles to specific organs and cell types: affinity moiety targeting and physicochemical tropism. Here we directly compare and combine both using intravenous (IV) lipid nanoparticles (LNPs) designed to target the lungs. We utilized PECAM antibodies as affinity moieties and cationic lipids for physicochemical tropism. These methods yield nearly identical lung uptake, but aPECAM LNPs show higher endothelial specificity. LNPs combining these targeting methods had >2-fold higher lung uptake than either method alone and markedly enhanced epithelial uptake. To determine if lung uptake is because the lungs are the first organ downstream of IV injection, we compared IV vs intra-arterial (IA) injection into the carotid artery, finding that IA combined-targeting LNPs achieve 35% of the injected dose per gram (%ID/g) in the first-pass organ, the brain, among the highest reported. Thus, combining the affinity moiety and physicochemical strategies provides benefits that neither targeting method achieves alone.

388 The First Endovascular Rat Glioma Model for Pre-clinical Evaluation of Intra-arterial Therapeutics

INTRODUCTION: Several translational animal models have been described assessing intra-arterial (IA) treatments for malignant gliomas. We describe the first endovascular animal model that allows testing of IA drug delivery as first-line treatment, which is difficult to do in actual patients. METHODS: Wistar rats underwent left femoral artery catherization with a Balt Magic 1.2F catheter or Marathon Flow directed 1.5F Microcatheter with an Asahi Chikai 0.008 micro-guidewire which was navigated to the left internal carotid artery under x-ray. 25% mannitol was administered to test blood brain barrier breakdown (BBBB). Additional rats were implanted with C6 glioma cells in the left frontal lobe. C6 Glioma-Implanted Rats were monitored for overall survival and tumor growth. Tumor volumes from MRI images were calculated utilizing 3D slicer. Additional rats underwent femoral artery catheterization with Bevacizumab, carboplatin, or irinotecan injected into the left internal carotid artery to test feasibility and safety. RESULTS: A successful endovascular access and BBBB protocol was established. BBBB was confirmed with positive Evans-blue staining. 10 rats were successfully implanted with C6 gliomas with confirmed growths on MRI. Overall survival was 19.75 ± 2.21 days. 5 rats were utilized for development of our femoral catheterization protocol and BBBB testing. With regards to IA chemotherapy dosage testing, control rats tolerated targeted 10 mg/kg of bevascizumab, 2.4 mg/kg of carboplatin, and 15 mg/kg of irinotecan IA ICA injections without complications. CONCLUSIONS: We present the first endovascular IA rat glioma model that allows selective catheterization of the intracranial vasculature and assessment of IA therapies for gliomas without need for access and sacrifice of proximal cerebrovasculature.

Intra-arterial PRRT with Lu-177 DOTATATE in Liver-dominant Metastatic Neuroendocrine Tumors: Early Assessment of Efficacy and Toxicity.

We proposed to administer Lu-177-DOTATATE in intra-arterial (IA) mode for higher first-pass localization to somatostatin receptors, higher residence time in liver metastases, and more radiation to tumor. This study aimed at assessing early hematological, renal and hepatotoxicity; and objective response to IA peptide receptor radionuclide therapy (PRRT). Fourteen patients (4 females and 10 males) were prospectively assessed. 5/14 patients underwent 2 cycles, whereas 3/14 underwent 3 cycles, and 6/14 received 1 cycle of IA PRRT. 200 mCi of Lu-177-DOTATATE was administered in 15-20 min by IA route under angiographic guidance. Patients were asked to follow-up at 4 and 8 weeks with hematological, liver, and renal functional parameters, and Ga-68 DOTATATE positron emission tomography/computed tomography (PET/CT) after 8 weeks. Response was assessed using RECIST 1.1 and EORTC PET criteria. Safety: 2/14 patients had high total and direct bilirubin, which reverted to normal after IA PRRT. Three patients had low albumin, which improved after 1 cycle. Nine patients showed no worsening of liver function. Two patients showed Grade 1 hematotoxicity which reverted to normal. Five patients showed high creatinine, but preserved glomerular filtration rate and EC clearance. On follow-up at 8 weeks, serum creatinine reverted to normal. Efficacy: In five patients who underwent 2 cycles of IA PRRT, 3 showed partial response (PR) on RECIST 1.1 and partial metabolic response (PMR) on EORTC criteria, whereas 2 showed stable disease (SD). In patients who underwent 3 cycles, 1 showed SD, whereas other patient showed PMR on DOTANOC PET/CT, with PR in size. Among the remaining seven patients, 5 showed PMR, whereas the other 2 showed SD. Thus 9/14 patients showed PR, whereas 5 showed SD on metabolic and size criteria. IA PRRT is a safe and efficacious approach for the treatment of liver dominant metastatic neuroendocrine tumors.

PRRT with Lu-177 DOTATATE in Treatment-Refractory Progressive Meningioma: Initial Experience from a Tertiary-Care Neuro-Oncology Center.

Refractory and/or recurrent meningiomas have poor outcomes, and the treatment options are limited. Peptide receptor radionuclide therapy (PRRT) has been used in this setting with promising results. We have documented our experience of using intravenous (IV) and intra-arterial (IA) approaches of Lu-177 DOTATATE PRRT. Eight patients with relapsed/refractory high-grade meningioma received PRRT with Lu-177 DOTATATE by IV and an IA route. At least 2 cycles were administered. Time to progression was calculated from the first PRRT session to progression. The response was assessed on MRI using RANO criteria, and visual analysis of uptake was done on Ga-68 DOTANOC PET/CT. Post-therapy dosimetry calculations for estimating the absorbed dose were performed. Median time to progression was 8.9 months. One patient showed disease progression, whereas seven patients showed stable disease at 4 weeks following 2 cycles of PRRT. Dosimetric analysis showed higher dose and retention time by IA approach. No significant peri-procedural or PRRT associated toxicity was seen. PRRT is a safe and effective therapeutic option for relapsed/refractory meningioma. The IA approach yields better dose delivery and should be routinely practised.

The impact of intraarterial, intravenous, and combined tirofiban on endovascular treatment for acute intracranial atherosclerotic occlusion.

Adjunctive tirofiban administration in patients undergoing endovascular treatment (EVT) for acute large vessel occlusion (LVO) has been investigated in several studies. However, the findings are conflict. This study aimed to compare the effect of different administration pathways of tirofiban on patients undergoing EVT for acute LVO with intracranial atherosclerotic disease (ICAD). Patients were selected from the ANGEL-ACT Registry (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke: A Prospective Multicenter Registry Study) and divided into four groups: intra-arterial (IA), intravenous (IV), and intra-arterial plus intravenous (IA+IV) and non-tirofiban. The primary outcome was 90-day ordinal modified Rankin Scale (mRS) score, and the secondary outcomes included the rates of mRS 0-1, 0-2, and 0-3 at 90-day, successful recanalization. The safety outcomes were symptomatic intracranial hemorrhage (sICH) and other safety endpoints. The multivariable logistic regression models adjusting for potential baseline confounders were performed to compare the outcomes. A propensity score matching (PSM) with a 1:1:1:1 ratio was conducted among four groups, and the outcomes were then compared in the post-matched population. A total of 502 patients were included, 80 of which were in the IA-tirofiban group, 73 in IV-tirofiban, 181 in (IA+IV)-tirofiban group, and 168 in the non-tirofiban group. The median (IQR) 90-day mRS score in the four groups of IA, IV, IA+IV, and non-tirofiban was, respectively 3(0-5) vs. 1(0-4) vs. 1(0-4) vs. 3(0-5). The adjusted common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.77 (95% CI, 0.45-1.30, P = 0.330), with IV-tirofiban vs. non-tirofiban was 1.36 (95% CI, 0.78-2.36, P = 0.276), and with (IA+IV)-tirofiban vs. non-tirofiban was 1.03 (95% CI, 0.64-1.64, P = 0.912). The adjusted OR for mRS 0-1 and mRS 0-2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.51 (95% CI, 0.27-0.98, P = 0.042) and 0.50 (95% CI, 0.26-0.94, P = 0.033). The other outcomes of each group were similar with non-tirofiban group, all P was >0.05. After PSM, the common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.41 (95% CI, 0.18-0.94, P = 0.036), and the OR for mRS 0-1 and mRS 0-2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.28 (95% CI, 0.11-0.74, P = 0.011) and 0.25 (95% CI, 0.09-0.67, P = 0.006). Intra-arterial administration of tirofiban was associated with worse outcome than non-tirofiban, which suggested that intra-arterial tirofiban had a harmful effect on patients undergoing EVT for ICAD-LVO. http://www.clinicaltrials.gov, Unique identifier: NCT03370939.

The safety and efficacy of intra-arterial low-dose tirofiban administration during endovascular therapy in patients with large ischemic core volume

This study aimed to evaluate the safety and efficacy of intra-arterial (IA) administration of low- dose tirofiban during endovascular therapy in patients with large ischemic core volumes on initial brain CT. Patients were divided into two groups based on the use of IA tirofiban. We identified 87 patients (16 and 71 patients in the tirofiban and no-tirofiban groups, respectively) with acute ischemic stroke due to intracranial artery occlusion who underwent endovascular therapy with a low Alberta Stroke Program Early CT scores (2–5). Multivariate logistic regression analysis revealed no association between IA tirofiban administration and serious postprocedural hemorrhagic complications (adjusted odds ratio (aOR), 0.720; 95% confidence interval (CI) 0.099–5.219; p = 0.960), any radiologic hemorrhage (aOR 0.076; 95% CI 0.003–2.323; p = 0.139), or 3-month mortality (aOR, 0.087; 95% CI 0.005–1.501; p = 0.093). However, IA tirofiban was associated with a lower 90-day mRS score (aOR, 0.197; 95% CI 0.015–1.306; p = 0.017) and change of NIHSS compared with baseline (aOR, 0.698; 95% CI 0.531–0.917; p = 0.010). IA tirofiban administration during endovascular therapy in patients with large ischemic core volumes may be effective and safe.

Abstract WMP111: Intra-Arterial Administration of Cerebral Endothelial Cell Derived Small Extracellular Vesicles Reduces Neurovascular Damage and Improves Neurological Outcome After Acute Ischemia in the Aged Rat

Stroke is a leading cause of death and disability worldwide, mainly affecting the elderly. Endovascular thrombectomy (EVT) is a standard of care therapy for stroke patients with large-vessel occlusion, however, the majority of these patients do not achieve full functional improvement. The present study tested the hypothesis that intra-arterial (IA) administration of cerebral endothelial cell derived small extracellular vesicles (CEC-sEVs) following transient middle cerebral artery occlusion (tMCAO) improves stroke outcome in the aged rat. CEC-sEVs (1x10 11 particles/injection) isolated from healthy adult rats were employed. Male aged rats (18 months, n=10/group) subjected to 3h tMCAO were randomly divided into the experimental groups. To examine whether IA injection of CEC-sEVs improves stroke outcome, CEC-sEVs were administered via the internal carotid artery (ICA) immediately following reperfusion by withdrawal of the occlusion filament. To examine whether intravenous administration (IV) of CEC-sEVs during tMCAO and then followed by IA CEC-sEVs upon reperfusion further enhances stroke outcome, CEC-sEVs were given at 30 min of tMCAO via a tail vein and upon reperfusion via the ICA. The ischemic rats treated with IA saline were used as a control. Neurological outcome and infarct volume were assessed in a blinded manner. IA CEC-sEVs upon reperfusion significantly reduced infarct volume (24±5% vs 31±6% in saline, p&lt;0.05) which was associated with robust improvement of neurological function from weeks 2 to 4 after tMCAO compared to saline treated rats. Moreover, rats treated with CEC-sEVs IV at 30min followed by IA treatment upon reperfusion further reduced infarct volume (16±6%) compared to rats treated with IA saline or CEC-sEVs. These rats also exhibited robust and early improvement of neurological function starting at 1d after tMCAO. In conclusion, IA administration of CEC-sEVs upon reperfusion significantly reduces ischemic damage, while an additional early (30min post stroke) dose of IV CEC-sEVs further enhances and accelerates the therapeutic effect of IA CEC-sEVs in the aged rats after tMCAO. Our data suggest that CEC-sEVs could potentially may be a therapy to amplify the efficacy of EVT even for elderly patients with acute ischemic stroke.

Abstract WP8: To Report the Visual Outcome and Safety Profile in Patients With Branch Retinal Artery Occlusion (BRAO) That Received Intravenous (IV) and Intra-Arterial (IA) Thrombolysis

Introduction: Branch retinal artery occlusion (BRAO) results from the blood flow compromise in of the branches of the central retinal artery. Data is limited on the outcome of patients with BRAO who received thrombolytic therapy as acute phase management protocol. Method: This study is a sub-analysis of our prior systematic review and meta-analysis on the visual outcome of patients with retinal artery occlusion who received intra-arterial (IA) or intra-venous (IV) thrombolytics within the first 24 hours. PubMed, Cochrane Library, ScienceDirect via Elsevier, International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and Trip Medical Database were systematically searched with a predefined protocol to record the change in the visual acuity (VA) after thrombolytic therapy. We limited this study to the patients with BRAO who received urokinase (UK) or tissue plasminogen activator (tPA). Results: Among 1153 identified studies, 771 patients with retinal artery occlusion received thrombolytic therapy. BRAO was observed in 19 patients (2.5%, mean age: 65 years). IAT-tPA was administered in 8 (42.1%), IVT-tPA in 7 (36.8%), and IVT-UK in 4 (21.1%). Median time from the onset of visual change to thrombolysis was 6.0 [4.5-10.5] hours. Patients had mean baseline logarithm of the Minimum Angle of Resolution (logMAR) of 0.9±0.8. VA improvement of ≥0.1 logMAR (one Snellen line) was seen among 17 (89.5%), VA improvement of ≥0.3 logMAR (three Snellen lines) among 13 (68.4%), and a final VA of 20/100 or better among 16 (84.2%). One (5.3%) patient had intra-ocular hemorrhage post thrombolysis. Conclusion: Compared to central retinal artery occlusion, patient with branched retinal occlusion have better visual recovery following IA or IV thrombolysis. These results can be affected by the small number of the patients in this study.

Intra-arterial Peptide Receptor Radionuclide Therapy for the Treatment of Hepatic Neuroendocrine Tumor Metastases: Hope or Hype?

Peptide receptor radionuclide therapy (PRRT) confers significant progression-free survival advantage for patients with small bowel grade 1 and 2 well-differentiated neuroendocrine tumors (WD NET). PRRT may also be clinically beneficial for patients with NET of pancreatic, bronchial, and other sites of origin; patients with paragangliomas; as well as for patients with well-differentiated grade 3 NET. Direct intra-arterial (IA) administration of PRRT into the hepatic artery for patients with NET liver metastases may result in higher radiopharmaceutical dose and longer dwell time in the liver tumors while relatively sparing non-tumor liver tissue and other organs such as the kidneys and bone marrow when compared with intravenous (IV) administration. This review summarizes currently available data on IA and IV PRRT dose distribution, reports safety and efficacy of IA PRRT, and proposes future research questions.

Abstract WMP88: Intraarterial Tirofiban Through Deployed Stent-Retriever Bailout: A Potential Alternative to Angioplasty and Stenting

Background: In stroke patients undergoing EVT, angioplasty and stenting (A&amp;S) has been described as a bailout technique when thrombectomy fails or intracranial stenosis is suspected. We aim to investigate effects of the administration of intraarterial (IA) tirofiban through a deployed stent-retriever over the occluding lesion prior to A&amp;S. Methods: Patients with LVO in the anterior circulation undergoing EVT were reviewed. We include patients in which stent-retriever/direct aspiration failed (TICI 0-2a) or underlying intracranial stenosis was suspected and received the loading dose of tirofiban prior to intended A&amp;S bailout. A stent-retriever was deployed over the lesion to create a by-pass channel and 8 to 12 ml of tirofiban were locally infused during 10 minutes through a distal access catheter proximally positioned. The stent-retriever was re-sheathed into the microcatheter before retrieval. Additionally, 10-15 ml of tirofiban were administered intravenously. An angiogram was performed to determine recanalization grade and indicate potential A&amp;S. Results: From 546 consecutive EVT patients, 14 (2.6%) were considered potential candidates for A&amp;S bailout and received the study protocol: mean age 76 years, median admission NIHSS 17 (IQR 11-21). The occlusion locations were: ICA (3, 21,4%), M1-MCA (9, 64.3%), M2-MCA (2, 14.3%), Mean IA tirofiban dose was 10mg. Post-infusion angiogram showed succesful reperfusion (TICI2b-3) in 11 patients (78.6%). In 4 cases (28.6%) A&amp;S was finally performed. At 24 hours median NIHSS was 14 (IQR 9-20) and the rates of reocclusion (follow-up imaging in 8/12) and SICH were 0%. Conclusion: In stroke patients undergoing EVT in which A&amp;S is considered as bailout, IA administration of tirofiban through a deployed stentretriever may safely achieve sustained recanalization in a substantial number of patients, ultimately avoiding definitive stenting. Further prospective data is warranted.

Safety Profile of Intra-Arterial Tirofiban as a Rescue Therapy during Mechanical Thrombectomy in Acute Ischemic Stroke

Abstract Purpose This article studies the safety profile and role of intra-arterial (IA) tirofiban as a rescue therapy in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy. Methods This is a retrospective observational study conducted among AIS patients with large vessel occlusion (LVO) eligible for endovascular revascularization and in whom IA tirofiban is given as rescue therapy. If the target vessel shows reocclusion following initial recanalization, flow limiting or significant residual stenosis after thrombectomy, or requires balloon angioplasty or stenting, IA tirofiban at a dose of 0.4 μg/kg/min was administered through the microcatheter in the target vessel followed by intravenous infusion of 0.1 μg/kg/min. The primary safety measure of the study was the incidence of symptomatic hemorrhage. Results The total number of patients in the study group was 82, 36 were in the tirofiban group and 46 were in the non-tirofiban group. Immediate successful reperfusion was achieved in 31 patients (86.1%) and 41 patients (89%) in the tirofiban and non-tirofiban groups, respectively. Note that 19.4 and 25% of patients in the tirofiban group required adjunct techniques of angioplasty and stenting, respectively. Also, 2.7% patient in the tirofiban group had a symptomatic hemorrhage, while 8.7% in the non-tirofiban group had symptomatic intracranial hemorrhage. On multinomial logistic regression, history of transient ischemic attack, truncal occlusion and watershed infarct pattern predicted the usage of IA tirofiban during mechanical thrombectomy. Conclusion Usage of IA tirofiban with or without adjunct techniques as a rescue therapy during mechanical thrombectomy in LVO improved recanalization rates without increasing the risk of symptomatic hemorrhage.

Quality of life following treatment with intra-arterial cisplatin with concurrent radiation and erlotinib for locally advanced head and neck cancer

ObjectivesStudies that focus on the feasibility of using erlotinib plus chemoradiation to treat locally advanced head and neck cancer have given hints of improved survival outcomes compared to chemoradiation alone. However, the influence of this treatment regimen on the quality of life of the patients has not been documented. We conducted a study of this triple combination and now have documented follow-up survival data as well as long-term quality of life (QoL) measures.MethodsThree sets of QoL questionnaires were given to patients with a diagnosis of head and neck cancer at two time points, pre- and post-treatment, to assess differences in quality of life after receiving chemotherapy with intra-arterial (IA) cisplatin (150 mg/m2), concomitant radiation (70 Gy), and oral erlotinib (150 mg/day). Additionally, patients were followed for a total of 5 years.ResultsTreatment had a detrimental effect on appearance, taste, and saliva domain scores in their QoL questionnaires. Nonetheless, fewer patients reported pain and anxiety.Significance of resultsThe combination of erlotinib with chemoradiation produced similar adverse effects on the QoL scores of patients with head and neck cancer as compared to chemoradiation alone.