Accuracy and precision assessment for activity quantification in individualized dosimetry of 177Lu-DOTATATE therapy

Background: In order to obtain a reliable 177Lu-DOTATATE therapy dosimetry, it is crucial to acquire accurate and precise activity measurements with the radionuclide calibrator, the SPECT/CT camera, and the NaI(Tl) well counter. The aim of this study was to determine, in a clinical context, the accuracy and the precision of their activity quantification over a range of activities and time. Ninety-three 177Lu sources from the manufacturer were measured in the radionuclide calibrator over 2.5 years to evaluate its calibration accuracy and precision compared to the manufacturer’s value. A NEMA 2012/IEC 2008 phantom was filled with a 177Lu activity concentration sphere-to-background ratio of five. It was acquired with the SPECT/CT camera to determine the reconstruction parameters offering the best compromise between partial volume effect and signal-to-noise ratio. The calibration factor was computed accordingly. The calibration quality was monitored over 2.5 years with 33 phantom acquisitions with activities ranging from 7040 to 0.6 MBq. Home-made sources were used to calibrate the well counter. Its reliability was evaluated with activities ranging from 150 to 0.2 kBq measured 34 times over 2.5 years. Results: For the radionuclide calibrator, median [interquartile range] for the error on activity measurement was −0.99 [1.31] %. The optimal SPECT reconstruction parameters were obtained with 16 iterations, 16 subsets and a 12-mm Gaussian post-filter. The calibration factor was 9.87 cps/MBq with an error of −1.05 [2.12] %. The well counter was calibrated with 31.5 cps/kBq, and the error was evaluated to −12.89 [16.55] %. Conclusions: The accuracy and the precision of activity quantification using dedicated quality control were found to be sufficient for use in dosimetry implemented in clinical routine. The proposed methodology could be implemented in other centres to obtain reproducible 177Lu-based treatment dosimetry.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Radiopeptide infusions of hepatic metastases after temporal implementation of an intra-arterial port system

On the course of the intra-arterial PRRT with 111In-DTPA0-Octreotide, often, due to the multiple (approximately 12) consecutive catheterizations, the femoral arteries get hardened; a port system ending at the proper hepatic artery is subcutaneously, temporarily implanted. The implantable port absolves the patients of the repeated discomfort due to the catheterization procedure and the obligatory 24 h-immobilization of the lower limb to avoid a possible hematoma, due to the preceded puncture of the femoral artery that the patient had to undergo for the hepatic artery catheterization. This port system offers stable connection mechanism at port chamber/catheter junction, high flow rate in thin catheters, secure placement of the puncture needle in the chamber septum, easy location of the puncture site, and quality of life. This chapter describes in detail the therapeutic scheme with repeated high doses of 111In-DTPA0-Octreotide, applied by means of this temporary implemented Intra-arterial Port System.SCOPUS: ch.binfo:eu-repo/semantics/publishe

131I-metaiodobenzylguanidine and peptide receptor radionuclide therapy in pheochromocytoma and paraganglioma

PURPOSE OF REVIEW: Pheochromocytomas and paragangliomas are rare tumors arising, respectively, from the adrenal medulla and extra-adrenal sympathetic or parasympathetic paraganglia. The main therapeutic objectives in case of metastatic disease are the reduction of tumor burden and the control of symptoms resulting from excessive catecholamine secretion. Treatment choices constitute not only a wait and see attitude, locoregional approaches, chemotherapy regiments but also radiopharmaceutical agents, and they should be discussed in a specialized multidisciplinary board. This review will briefly discuss the radiopharmaceutical modalities in patients with pheochromocytomas and paragangliomas (I-MIBG and PRRT). RECENT FINDINGS: I-MIBG (Azedra) has received FDA approval for patients with iobenguane-scan-positive, unresectable, locally advanced or metastatic pheochromocytomas and paragangliomas who require systemic anticancer therapy, whereas peptide receptor radionuclide therapy using radiolabelled somatostatin analogues is currently performed in compassionate use, with very promising results. No prospective head-to-head comparison between the modalities has been conducted to date. SUMMARY: Promising results have been reported for both radiopharmaceutical agents, mostly in the setting of retrospective series. No prospective head-to-head comparison between the modalities is yet available.SCOPUS: ar.jDecretOANoAutActifinfo:eu-repo/semantics/publishe

Intra-arterial therapeutic approach of hepatic neuroendocrine character neoplasiae with 111indium-pentetreotide after temporary installation of a catheter - port system

Purpose: To evaluate the effectiveness of high doses of 111Ιn-DTPA‐OCinfusions following selective catheterization of the hepatic artery throughout atemporary port installation in inoperable liver metastasized, SSTR2 positive neuroendocrinetumours due to the effect of 111Ιn Auger and Internal Conversion ElectronEmission.Materials and Methods: The average dose per session administeredmonthly to each patient (9 cases in total) was 6.3±2.3 GBq. Since repeatitions raisedthe 12 fold in order to exempt patients from the repeated catheterizationprocedure discomfort, a temporary intraarterial installation of a specificcatheterization port system was performed. Response assessment was classifiedaccording to the Response Evaluating Criteria In Solid Tumours (RECIST). CT/MRIscans were performed as baseline before, during and after the end of treatment andmonthly US images for follow up measurements. Toxicity (WHO criteria) wasmeasured using blood and urine tests of renal, hepatic and bone marrow function.Results: No one from the treated patients [108 infusions] achieved completeresponse [CR: 0.0%] , partial response [PR] was observed in 7 (70 %) and diseasestabilization[SD] in 2 ( 30 %) patients. Dosimetric calculations showed an about 75%(p<0.05) higher radiopeptide cumulative dose compared to that of the simpleintravenous administration. Grade 1 erythro-, leuko- and thrombo- cytopeniaoccurred in 3 (34.0 %) cases.Conclusion: In unresectable metastatic liver lesions, positive for somatostatinreceptors repeated, trans‐hepatic, high doses of 111Ιn-DTPA‐OC throughout atemporary port installation, showed an effective therapeutic outcome. Given thelocoregional modality character of the administration technique after the temporaryport installation for the completion of the treatment plus the extremely short range of111Ιn Auger and Internal Conversion electrons emission, no nephro-, liver- or myelotoxicityhas so far been observed. The implantable port system offers stable connection mechanism at port chamber/catheter junction, high flow rate in thincatheters, secure placement of the puncture needle in the chamber septum, easylocation of the puncture site and quality of life.Σκοπός: Για να αξιολογηθεί η αποτελεσματικότητα εγχύσεων υψηλών δόσεων111Ιn-DTPA‐OC μετά από επιλεκτικό καθετηριασμό της ηπατικής αρτηρίας, διαμέσουπροσωρινής τοποθέτησης ειδικού καθετηριαστικού συστήματος (port) σε μηλειτουργικούς νευροενδοκρινούς χαρακτήρα, ηπατικές μεταστάσεις, θετικούς σευποδοχείς SSTR2 σωματοστατίνης από την επίδραση της εκπομπής ηλεκτρονίων Augerκαι Εσωτερικής Μετατροπής του 111Ιn.Υλικά και Μέθοδοι: Η χορηγούμενη μέση δόση ανά συνεδρία, μηνιαίως για κάθεασθενή (9 περιπτώσεις συνολικά) ήταν 6,3±2,3 GBq. Επειδή οι επαναλαμβανόμενεςχορηγήσεις για μια αποτελεσματική αγωγή έφθαναν τις 12 στο σύνολό τους,προκειμένου να απαλλαγούν οι ασθενείς από την κακουχία και δυσφορία τηςδιαδικασίας του καθετηριασμού, απεφασίσθη η προσωρινή ενδο‐αρτηριακήεγκατάσταση ενός ειδικού καθετηριαστικού συστήματος port. Η αξιολόγηση τηςανταπόκρισης στο θεραπευτικό σχήμα εγένετο σύμφωνα με τα κριτήρια RECIST γιασυμπαγείς όγκους. Το αποτέλεσμα επιστοποιείτο από τις CT ή MRI τομογραφίες πουπραγματοποιούντο πριν, κατά τη διάρκεια και μετά το τέλος της θεραπείας, ενώ ηπαρακολούθηση εκτιμάτο απο τα μηνιαία υπερηχογραφήματα στις περιοχέςενδιαφέροντος. Η πιθανή τοξικότητα (WHO κριτήρια) μετρήθηκε από δείγματα αίματοςκαι ούρων και από ελέγχους της νεφρικής, ηπατικής και οστεομυελικής λειτουργίας.Αποτελέσματα: Κανείς από τους ασθενείς που έλαβαν θεραπεία [108 εγχύσεις]επέτυχε πλήρη ανταπόκριση [CR: 0,0%]. Μερική ανταπόκριση [PR] παρατηρήθηκε σε7 (70%) και σταθεροποίηση της νόσου [SD] σε 2 (30%) ασθενείς. Δοσιμετρικοίυπολογισμοί έδειξαν περίπου 75% (p<0,05) υψηλότερη αθροιστική ραδιοπεπτιδικήαπρρόφηση, σε σύγκριση με εκείνη της απλής ενδοφλέβιας χορήγησης. Πρώτουβαθμού μυελοτοξικότητα (ερυθρο-, λευκο- και θρομβο- πενία παρατηρήθηκε σε 3(34,0%) περιπτώσεις.Συμπέρασμα: Σε μη χειρουργήσιμες νεοπλασίες του ήπατος, σπινθηρογραφικάθετικές σε SSTR2 υποδοχείς σωματοστατίνης η επαναλαμβανόμενη δι‐ηπατική χορήγηση, υψηλών δόσεων 111Ιn-DTPA‐OC διαμέσου προσωρινά τοποθετημένουκαθετηριαστικού συστήματος port, είχε περισσότερο από ικανοποιητικήαποτελεσματική θεραπευτική έκβαση. Με δεδομένο τον τοποπεριοχικό χαρακτήρα τηςαγωγής, μετά από προσωρινή εγκατάσταση καθετηριαστικού συστήματος port γιατην ολοκλήρωση της θεραπείας και την εξαιρετικά μικρή εμβέλεια των ηλεκτρονίωνAuger και Εσωτερικής Μετατροπής του 111Ιn, δεν έχει παρατηρηθεί μέχρι σήμερακάποια νεφρική, ηπατική ή οστεομυελική τοξικότητα. Η προσωρινά ενδαρτηριακήεμφύτευση ειδικού καθετηριαστικού συστήματος port προσφέρει σταθερό μηχανισμόσύνδεσης υποδορροίου τυμπάνου‐καθετήρα‐όγκου, υψηλό ρυθμό ροής σε λεπτόδίαυλο, ασφαλή και ανώδυνη εισαγωγή της βελόνας παρακέντησης στο διάφραγμασιλικόνης του θαλάμου και ποιότητα ζωής

Acute Pancreatitis Following Peptide Receptor Radionuclide Therapy: An Unusual Adverse Event

A 54-year-old man with grade 2 rectal neuroendocrine tumor and hepatic, pancreatic, and bone metastases was treated with 177Lu-DOTATATE as second-line therapy, after failure of somatostatin analogues. Two weeks after the first injection, he presented at the emergency department with acute pancreatitis. We hypothesized that this unusual adverse event, never been reported so far, was the result of acute tumor irradiation after PRRT, leading to peritumoral inflammation and edema with obstruction of an accessory pancreatic duct.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Mantle cell lymphoma simulating inflammatory bowel disease.

We report a case of colorectal involvement by a mantle cell lymphoma (MCL) that had been considered before as inflammatory bowel disease. Diagnosis of low-grade MCL can be difficult, and here we highlight the importance of thorough histopathological examination in case of supposed inflammatory bowel disease that does not react to therapy.info:eu-repo/semantics/publishe

Unusual diffuse liver 18F-FDG uptake in melanoma patient treated by ipilimumab

We present herein a case of unusual 18F-FDG PET-CT diffuse hypermetabolic liver uptake in melanoma patient treated by ipilimumab.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Suspicious cold thyroid nodule with intense focal 68Ga-DOTATATE uptake: a case report.

A 51-year-old male was found with bilateral thyroid nodules on ultrasonography neck imaging. The largest nodule, measuring 23 × 26 × 35 mm, was located in the left lobe and was classified as EU-TIRADS 4. Thyroid function tests were normal, as were serum levels of parathormone, Chromogranin A, carcinoembryonic antigen and calcitonin. The nodule was cold on thyroid scintigraphy. Fine-needle aspiration of the nodule did not demonstrate cellular atypia. High focal uptake was found on both 111In-DTPA-octreotide scintigraphy and 68Ga-DOTATATE PET/CT. Histopathological analysis showed a microfollicular adenoma without malignancy. Immunohistochemical staining did not suggest neuroendocrine neoplasia or C cell hyperplasia. However, high expression of somatostatin receptor 2 (SSTR2) was observed in the microfollicular adenoma compared to the surrounding healthy tissue, with predominant localization in the endothelial cells and at the secretory pole of the thyroid epithelial cells in contact with blood vessels. High focal thyroid uptake on 68Ga-DOTATATE PET/CT can be observed in benign thyroid nodules due to an overexpression of SSTR by endothelial cells. However, incidental focal thyroid uptake on SSTR imaging requires further investigations to rule out thyroid malignancy.info:eu-repo/semantics/publishe

A dosimetry procedure for organs-at-risk in 177Lu peptide receptor radionuclide therapy of patients with neuroendocrine tumours

Purpose: Peptide receptor radionuclide therapy with 177Lu-DOTATATE has become a standard treatment modality in neuroendocrine tumours (NETs). No consensus has yet been reached however regarding the absorbed dose threshold for lesion response, the absorbed dose limit to organs-at-risk, and the optimal fractionation and activity to be administered. This is partly due to a lack of uniform and comparable dosimetry protocols. The present article details the development of an organ-at-risk dosimetry procedure, which could be implemented and used routinely in a clinical context. Methods: Forty-seven patients with NETs underwent 177Lu-DOTATATE therapy. Three SPECT/CT images were acquired at 4, 24 and 144–192 h post-injection. Three blood samples were obtained together with the SPECT/CT acquisitions and 2 additional samples were obtained around 30 min and 1 h post-injection. A bi-exponential fit was used to compute the source organ time-integrated activity coefficients. Coefficients were introduced into OLINDA/EXM software to compute organ-at-risk absorbed doses. Median values for all patients were computed for absorbed dose coefficient D/A0 and for late effective half-life T1/2eff for kidneys, spleen and red marrow. Results: Dosimetry resulted in a median[interquartile range] of 0.78[0.35], 1.07[0.58] and 0.028[0.010] Gy/GBq for D/A0 and of 55[9], 71[9] and 52[18] h for T1/2eff for kidneys, spleen and red marrow respectively. Conclusions: A dosimetry procedure for organs-at-risk in 177Lu-DOTATATE therapy based on serial SPECT/CT images and blood samples can be implemented routinely in a clinical context with limited patient burden. The results obtained were in accordance with those of other centres.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Tumor Volume on PSMA PET as a Prognostic Biomarker in Prostate Cancer Patients Treated With Cabazitaxel.

The aim of this study was to evaluate the prognostic value of 68 Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT in metastatic castration-resistant prostate cancer patients receiving second-line chemotherapy with cabazitaxel.info:eu-repo/semantics/publishe