Toxicity and efficacy profiles of intrathecal injection of I-131 NaI via intraventricular (IVent) or intralumbar (Ilumb) route for leptomeningeal metastases (LM) therapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1549-1549
Author(s):  
F. C. Wong ◽  
M. Groves ◽  
N. Papadopoulos ◽  
S. Kim ◽  
C. Conrad ◽  
...  
Keyword(s):  
Intrathecal Injection ◽  
Intrathecal Chemotherapy ◽  
Whole Body ◽  
Csf Cytology ◽  
Two Phase ◽  
External Beam Irradiation ◽  
Red Marrow ◽  
Lugol Solution ◽  
Grade Ii ◽  
Low Toxicity

1549 Background: LM is a fatal complication occurring in up to 30% of cancer patients. Intrathecal chemotherapy of LM is limited by diffusion while external beam irradiation is limited by neurotoxicity. Radioiodine I-131 may serve as a ablating agent because of its radiations transverse the meningeal thinkness but spare distant underlying nervous tissues. Two phase I studies are designed to determine MTD and to evaluate potential toxicity and efficacy of intrathecal I-131 sodium iodide (NaI) injected via IVent or the ILumb route. Methods: The IVent or Ilumb protocols each accured 5 groups of patients with cytology-confirmed LM from solid tumors. An injection of 15, 30, 60, 90 or 120 mCi of I-131 NaI was performed after thyroid blockade (Lugol solution and perchlorate), via an Ommaya reservoir (IVent) or lumbar puncture (ILumb). Patients underwent whole-body scintigraphy for biodistribution and radiation dosimetry. Follow-up studies consisted of serial CSF cytology, neuropsychology, ophthalmology, and serum tests (TSH and CBC) to 6 months. Results: The IVent and Ilumb studies accured 16 and 15 patients respectively with LM from melanoma, lung, breast and other tumors (13, 8, 6 and 4 of 31 patients). Because of re-entry into the protocols, one patient received a total of 407 mCi; the maximum radiation absorbed doses were estimated at 3716 cGy in the ventricular CSF and 54 cGy in the red marrow. No treatment-related NCI-Grade II/III/IV neurologic, hematologic or thyroid toxicity is noted. Transient improvements up to 6 weeks are noted in neuropsychologic tests (5/16 and 5/15), ophthalomologic test (3/16 and 1/15) and CSF cytology conversion (to negative) in 5/16 and 4/15 patients, respectively. Electrophysiology tests of 2 patients demonstrated normalization of P37 waves measured by somatosensory evoked potentials along with neuropsychologic test improvements. Conclusions: The MTD has not been reached up to 120 mCi on either the IVent or Ilumb protocol. Intrathecal I-131 NaI is likely to be efficacious to eradicate tumors in the CSF for LM therapy. Because of the low toxicity and likely efficacy, a phase II study with higher dosages is needed to fully explore therapeutic potentials of intrathecal I-131 NaI. No significant financial relationships to disclose.

Diagnostic challenges in neoplastic meningitis presenting as intracranial hypertension

2021 ◽  
Vol 14 (3) ◽  
pp. e238808
Author(s):  
Santosh Sriram Andugulapati ◽  
Akash Chheda ◽  
Karan Desai ◽  
Sangeeta Hasmukh Ravat
Keyword(s):  
Cerebrospinal Fluid ◽  
Intracranial Hypertension ◽  
Neoplastic Meningitis ◽  
Whole Body ◽  
Csf Cytology ◽  
Csf Analysis ◽  
Pet Ct ◽  
Pet Ct Scan ◽  
Systemic Malignancy

A diagnosis of idiopathic intracranial hypertension should be considered only after careful exclusion of all possible aetiologies. We report a case of neoplastic meningitis presenting as intracranial hypertension with inconclusive repeated cerebrospinal fluid (CSF) cytology and MRI of brain, emphasising the importance of meticulous CSF analysis and role of early whole-body PET–CT scan for diagnosis of systemic malignancy.

scholarly journals Low-toxicity FePt nanoparticles for the targeted and enhanced diagnosis of breast tumors using few centimeters deep whole-body photoacoustic imaging

2020 ◽  
Vol 19 ◽  
pp. 100179
Author(s):  
Yubin Liu ◽  
Pei-Chun Wu ◽  
Sen Guo ◽  
Pi-Tai Chou ◽  
Chuxia Deng ◽  
...  
Keyword(s):  
Photoacoustic Imaging ◽  
Breast Tumors ◽  
Whole Body ◽  
Fept Nanoparticles ◽  
Low Toxicity

scholarly journals Preclinical Incorporation Dosimetry of [18F]FACH—A Novel 18F-Labeled MCT1/MCT4 Lactate Transporter Inhibitor for Imaging Cancer Metabolism with PET

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2024 ◽  
Author(s):  
Bernhard Sattler ◽  
Mathias Kranz ◽  
Barbara Wenzel ◽  
Nalin T. Jain ◽  
Rareş-Petru Moldovan ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Urinary Bladder ◽  
Cancer Metabolism ◽  
Emission Tomography ◽  
Whole Body ◽  
Organ Doses ◽  
Time Activity ◽  
Weighting Factors ◽  
Red Marrow ◽  
Positron Emission

Overexpression of monocarboxylate transporters (MCTs) has been shown for a variety of human cancers (e.g., colon, brain, breast, and kidney) and inhibition resulted in intracellular lactate accumulation, acidosis, and cell death. Thus, MCTs are promising targets to investigate tumor cancer metabolism with positron emission tomography (PET). Here, the organ doses (ODs) and the effective dose (ED) of the first 18F-labeled MCT1/MCT4 inhibitor were estimated in juvenile pigs. Whole-body dosimetry was performed in three piglets (age: ~6 weeks, weight: ~13–15 kg). The animals were anesthetized and subjected to sequential hybrid Positron Emission Tomography and Computed Tomography (PET/CT) up to 5 h after an intravenous (iv) injection of 156 ± 54 MBq [18F]FACH. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time–activity data. Time and mass scales were adapted to the human order of magnitude and the ODs calculated using the ICRP 89 adult male phantom with OLINDA 2.1. The ED was calculated using tissue weighting factors as published in Publication 103 of the International Commission of Radiation Protection (ICRP103). The highest organ dose was received by the urinary bladder (62.6 ± 28.9 µSv/MBq), followed by the gall bladder (50.4 ± 37.5 µSv/MBq) and the pancreas (30.5 ± 27.3 µSv/MBq). The highest contribution to the ED was by the urinary bladder (2.5 ± 1.1 µSv/MBq), followed by the red marrow (1.7 ± 0.3 µSv/MBq) and the stomach (1.3 ± 0.4 µSv/MBq). According to this preclinical analysis, the ED to humans is 12.4 µSv/MBq when applying the ICRP103 tissue weighting factors. Taking into account that preclinical dosimetry underestimates the dose to humans by up to 40%, the conversion factor applied for estimation of the ED to humans would rise to 20.6 µSv/MBq. In this case, the ED to humans upon an iv application of ~300 MBq [18F]FACH would be about 6.2 mSv. This risk assessment encourages the translation of [18F]FACH into clinical study phases and the further investigation of its potential as a clinical tool for cancer imaging with PET.

scholarly journals Biodistribution and dosimetry of a single dose of albumin-binding ligand [177Lu]Lu-PSMA-ALB-56 in patients with mCRPC

2020 ◽  
Author(s):  
Vasko Kramer ◽  
René Fernández ◽  
Wencke Lehnert ◽  
Luis David Jiménez-Franco ◽  
Cristian Soza-Ried ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Whole Body ◽  
Published Data ◽  
Albumin Binding ◽  
Castration Resistant Prostate Cancer ◽  
Effective Treatment Option ◽  
Binding Properties ◽  
Castration Resistant ◽  
Red Marrow ◽  
Therapeutic Outcomes

Abstract Introduction PSMA-targeted radionuclide therapy with lutetium-177 has emerged as an effective treatment option for metastatic, castration-resistant prostate cancer (mCRPC). Recently, the concept of modifying PSMA radioligands with an albumin-binding entity was demonstrated as a promising measure to increase the tumor uptake in preclinical experiments. The aim of this study was to translate the concept to a clinical setting and evaluate the safety and dosimetry of [177Lu]Lu-PSMA-ALB-56, a novel PSMA radioligand with albumin-binding properties. Methods Ten patients (71.8 ± 8.2 years) with mCRPC received an activity of 3360 ± 393 MBq (120–160 μg) [177Lu]Lu-PSMA-ALB-56 followed by whole-body SPECT/CT imaging over 7 days. Volumes of interest were defined on the SPECT/CT images for dosimetric evaluation for healthy tissue and tumor lesions. General safety and therapeutic efficacy were assessed by measuring blood biomarkers. Results [177Lu]Lu-PSMA-ALB-56 was well tolerated, and no severe adverse events were observed. SPECT images revealed longer circulation of [177Lu]Lu-PSMA-ALB-56 in the blood with the highest uptake in tumor lesions at 48 h post injection. Compared with published data for other therapeutic PSMA radioligands (e.g. PSMA-617 and PSMA I&T), normalized absorbed doses of [177Lu]Lu-PSMA-ALB-56 were up to 2.3-fold higher in tumor lesions (6.64 ± 6.92 Gy/GBq) and similar in salivary glands (0.87 ± 0.43 Gy/GBq). Doses to the kidneys and red marrow (2.54 ± 0.94 Gy/GBq and 0.29 ± 0.07 Gy/GBq, respectively) were increased. Conclusion Our data demonstrated that the concept of albumin-binding PSMA-radioligands is feasible and leads to increased tumor doses. After further optimization of the ligand design, the therapeutic outcomes may be improved for patients with prostate cancer.

Whole body autoradiography of mice after intrathecal injection of morphine

Pain ◽  
1984 ◽  
Vol 18 ◽  
pp. S231
Author(s):  
L. L. Gustafsson ◽  
C. Post ◽  
A. Bonnevier ◽  
H.-C. Ramsay
Keyword(s):  
Intrathecal Injection ◽  
Whole Body ◽  
Whole Body Autoradiography

scholarly journals Pivotal Role of Dosimetry in High Activity 131i Mibg Therapy in Patients Affected by High Risk Relapsed Refractory Neuroblastoma: Towards a Deeper Metastatic Response Understanding

2021 ◽  
Author(s):  
Bartolomeo Cassano ◽  
Milena Pizzoferro ◽  
Silvio Valeri ◽  
Claudia Polito ◽  
Salvatore Donatiello ◽  
...  
Keyword(s):  
High Risk ◽  
Clinical Outcome ◽  
High Activity ◽  
Absorbed Dose ◽  
Complete Response ◽  
Whole Body ◽  
High Dose ◽  
Red Marrow ◽  
Activity Therapy ◽  
Mibg Therapy

Abstract Background: Dosimetry in molecular radiotherapy for personalized treatment is assuming a central role in clinical management of aggressive/relapsed tumors. High-Risk relapsed/refractory metastatic Neuroblastoma (HRrrm-NBL) has a poor prognosis and high-activity 131I-mIBG therapy could represent a promising strategy.The aim of this study was to report the absorbed dose to whole-body (DWB), red marrow (DRM) and lesions (DLesion) correlated to clinical outcome.Methods: 14 patients affected by HRrrm-NBL were treated with high-activity 131I-mIBG therapy (two administrations separated by 15 days). The first administration was weight-based whereas the second one was dosimetry-based (achieving 4 Gy to whole-body). In all patients DWB and DRM has been assessed; 9/14 patients were selected for DLesion evaluation (for a total of 13 lesions). Treatment response was classified in Progression and Stable Disease (PD and SD), Partial and Complete Response (PR and CR) and correlated to the value of DLesion value.Results: The cumulative DWB, DRM and DLesion ranged from [1.49; 4.45], [0.99; 2.56] and [44.17; 585.75] Gy. After treatment 3, 2, 4 and 5 patients showed CR, PR, SD and PD respectively showing a correlation between the clinical outcome and DLesion with a threshold at 80 Gy.Conclusions: Our experience shows feasibility of high activity therapy of 131I MIBG in rrmHR-NBL children as two administration intensive strategy. Dosimetric approach allowed a tailored high dose treatment maximizing the benefits of radionuclide therapy for pediatric patients with a safety profile. The assesment of DLesion contributed to have a deeper understaning of metabolic treatment effects.

scholarly journals Dosimetry of 177Lu-PSMA-617 after Mannitol Infusion and Glutamate Tablet Administration: Preliminary Results of EUDRACT/RSO 2016-002732-32 IRST Protocol

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 621 ◽  
Author(s):  
Anna Sarnelli ◽  
Maria Belli ◽  
Valentina Di Iorio ◽  
Emilio Mezzenga ◽  
Monica Celli ◽  
...  
Keyword(s):  
Dose Calculation ◽  
Whole Body ◽  
Castration Resistant Prostate Cancer ◽  
Parotid Glands ◽  
Castration Resistant ◽  
Red Marrow ◽  
Dosimetric Data ◽  
Significant Difference ◽  
Post Infusion ◽  
Prospective Phase

Radio-ligand therapy (RLT) with177Lu-PSMA-617 is a promising option for patients with metastatic castration-resistant prostate-cancer (mCRPC). A prospective phase-II study (EUDRACT/RSO,2016-002732-32) on mCRPC is ongoing at IRST (Meldola, Italy). A total of 9 patients (median age: 68 y, range: 53–85) were enrolled for dosimetry evaluation of parotid glands (PGs), kidneys, red marrow (RM) and whole body (WB). Folic polyglutamate tablets were orally administered as PGs protectors and 500 mL of a 10% mannitol solution was intravenously infused to reduce kidney uptake. The whole body planar image (WBI) and blood samples were acquired at different times post infusion (1 h, 16–24 h, 36–48 h and 120 h). Dose calculation was performed with MIRD formalism (OLINDA/EXM software). The median effective half-life was 33.0 h (range: 25.6–60.7) for PGs, 31.4 h (12.2–80.6) for kidneys, 8.2 h (2.5–14.7) for RM and 40.1 h (31.6–79.7) for WB. The median doses were 0.48 mGy/MBq (range: 0.33–2.63) for PGs, 0.70 mGy/MBq (0.26–1.07) for kidneys, 0.044 mGy/MBq (0.023–0.067) for RM and 0.04 mGy/MBq (0.02–0.11) for WB. A comparison with previously published dosimetric data was performed and a significant difference was found for PGs while no significant difference was observed for the kidneys. For PGs, the possibility of reducing uptake by administering glutamate tablets during RLT seems feasible while further research is warranted for a more focused evaluation of the reduction in kidney uptake.

Meningioma metastases: incidence and proposed screening paradigm

2020 ◽  
Vol 132 (5) ◽  
pp. 1447-1455 ◽  
Author(s):  
Cecilia L. Dalle Ore ◽  
Stephen T. Magill ◽  
Adam J. Yen ◽  
Maryam N. Shahin ◽  
David S. Lee ◽  
...  
Keyword(s):  
Significant Proportion ◽  
Ct Scanning ◽  
Additional Treatment ◽  
Whole Body ◽  
Who Grade ◽  
Recurrent Meningioma ◽  
Number Needed To Screen ◽  
Grade Ii ◽  
Grade Iii

OBJECTIVEExtracranial meningioma metastases are uncommon, occurring in less than 1% of patients diagnosed with meningioma. Due to the rarity of meningioma metastases, patients are not routinely screened for distant disease. In this series, we report their experience with meningioma metastases and results of screening for metastases in select patients with recurrent meningiomas.METHODSAll patients undergoing resection or stereotactic radiosurgery for primary or recurrent meningioma from 2009 to 2017 at a single center were retrospectively reviewed to identify patients who were diagnosed with or underwent imaging to evaluate for systemic metastases. Imaging to evaluate for metastases was performed with CT scanning of the chest, abdomen, and pelvis or whole-body PET/CT using either FDG or 68Ga-DOTA-octreotate (DOTATATE) tracers in 28 patients. Indications for imaging were symptomatic lesions concerning for metastasis or asymptomatic screening in patients with greater than 2 recurrences being evaluated for additional treatment.RESULTSOf 1193 patients treated for meningioma, 922 (77.3%) patients had confirmed or presumed WHO grade I tumors, 236 (19.8%) had grade II tumors, and 35 (2.9%) had grade III tumors. Mean follow-up was 4.3 years. A total of 207 patients experienced recurrences (17.4%), with a mean of 1.8 recurrences. Imaging for metastases was performed in 28 patients; 1 metastasis was grade I (3.6%), 16 were grade II (57.1%), and 11 were grade III (39.3%). Five patients (17.9%) underwent imaging because of symptomatic lesions. Of the 28 patients screened, 27 patients had prior recurrent meningioma (96.4%), with a median of 3 recurrences. On imaging, 10 patients had extracranial lesions suspicious for metastasis (35.7%). At biopsy, 8 were meningioma metastases, 1 was a nonmeningioma malignancy, and 1 patient was lost to follow-up prior to biopsy. Biopsy-confirmed metastases occurred in the liver (5), lung (3), mediastinum (1), and bone (1). The observed incidence of metastases was 0.67% (n = 8). Incidence increased to 2% of WHO grade II and 8.6% of grade III meningiomas. Using the proposed indications for screening, the number needed to screen to identify one patient with biopsy-confirmed malignancy was 3.83.CONCLUSIONSSystemic imaging of patients with multiply recurrent meningioma or symptoms concerning for metastasis may identify extracranial metastases in a significant proportion of patients and can inform decision making for additional treatments.

Central Nervous System Involvement in Non-Hodgkin's Lymphomas: Value of Lumbar Puncture as Initial Staging Procedure

1981 ◽  
Vol 67 (3) ◽  
pp. 197-202 ◽  
Author(s):  
Silvio Monfardini ◽  
Giuseppe Ficarra ◽  
Roberto Giardini ◽  
Armando Santoro
Keyword(s):  
Lumbar Puncture ◽  
Systemic Disease ◽  
Clinical Signs ◽  
Central Nervous System Involvement ◽  
Intrathecal Chemotherapy ◽  
Brain Parenchyma ◽  
Csf Cytology ◽  
Cns Involvement ◽  
Cns Relapse ◽  
Hodgkin's Lymphomas

To identify the subgroups of patients with malignant non-Hodgkin's lymphomas who might benefit from prophylactic therapy to prevent CNS relapse, lumbar puncture was routinely performed among the other staging procedures from January 1976 to October 1979 in 76 patients with diffuse lymphomas. The study also takes into consideration 32 patients who came to our observation during the same period and who were studied with lumbar puncture performed in case of suspicious CNS involvement or along with other procedures during restaging to acquire further information on prognostic factors related to CNS involvement. Cerebrospinal fluid (CSF) cytology was positive in 3 of 76 patients studied with initial lumbar puncture; however, only 2 (2.6 %) were asymptomatic. Within the group of 32 patients in whom lumbar puncture was performed during the course of the disease, all 17 patients with suspicious CNS involvement were found to have a positive CSF cytology with the exception of 1 patient with multiple focal involvement of brain parenchyma. Clinical signs of CNS involvement associated with CSF positivity were all found in patients with diffuse histology. In these patients bone marrow invasion or a leukemic picture was frequently associated with CNS relapse. In 47 % of patients CNS disease developed while they were in clinical remission. In this series cranio-spinal irradiation associated with intrathecal chemotherapy provided the best results, even if survival was not primarily dependent upon the control of their CNS involvement but related to progressive systemic disease in other sites. On the basis of the clinico-prognostic parameters examined, some guidelines for early diagnosis and treatment of CNS lymphomatous involvement are provided.

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