Publications by authors named "Jolanta Kunikowska"

67 Publications

Dose escalation study of targeted alpha therapy with [Ac]Ac-DOTA-substance P in recurrence glioblastoma - safety and efficacy.

Eur J Nucl Med Mol Imaging 2021 Apr 15. Epub 2021 Apr 15.

European Commission, Joint Research Centre, Directorate for Nuclear Safety and Security, Karlsruhe, Germany.

Glioblastoma is the most common and malignant primary brain tumour, with a poor prognosis. Introduction of new treatment options is critically important. The study aimed to assess the appropriateness of escalation doses and toxicity of [Ac]Ac-DOTA-SP therapy.

Material And Methods: A total of 21 patients (age of 43.0 ± 9.5 years), with histologically confirmed recurrent or conversion glioblastoma grade 4 following a standard therapy, have been included in the study. One to 2 intracavitary port-a-cath systems were stereotactically inserted. Patients were treated with escalation dose protocol with 10, 20 and 30 MBq per cycle totally 1-6 doses of [Ac]Ac-DOTA-SP in 2-month intervals. Therapeutic response was monitored by clinical performance status and MRI imaging.

Results: Treatment was well tolerated with mostly mild temporary adverse effects (oedema, epileptic seizures, aphasia, hemiparesis) mainly in the group of patients treated with 30 MBq of [Ac]Ac-DOTA-SP. Only one patient treated with 30 MBq revealed thrombopenia grade 3. There was no other grade 3 and 4 toxicity related to [Ac]Ac-DOTA-treatment in all groups. The median overall survival time from the primary diagnosis (OS-d) was 35.0 months and from the diagnosis of the recurrence/conversion (OS-r/c) was 13.2 months. From the start of treatment with [Ac]Ac-DOTA-SP, the median PFS was 2.4 months, and the OS-t was 9.0 months. There were no statistically significant differences between the investigated dose escalation groups.

Conclusions: Treatment of recurrent glioblastoma with [Ac]Ac-DOTA-SP is safe and well tolerated up to 30 MBq per cycle. The escalation dose protocol showed good tolerability. Only mild temporary adverse effects were observed. No remarkable haematological, kidney and liver toxicity was seen.
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http://dx.doi.org/10.1007/s00259-021-05350-yDOI Listing
April 2021

A rare cause of chronic diarrhoea: a diagnosis to keep in mind.

Endokrynol Pol 2021 22;72(2):187-188. Epub 2021 Mar 22.

Department of Gastroenterology, Pomeranian Medical University, Szczecin, Poland.

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http://dx.doi.org/10.5603/EP.a2021.0020DOI Listing
March 2021

EANM Focus 3: The International Conference on Molecular Imaging and Theranostics in Neuroendocrine Tumours-the consensus in a nutshell.

Eur J Nucl Med Mol Imaging 2021 May;48(5):1276-1277

Department of Nuclear Medicine, Universitätsklinikum, Essen, Germany.

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http://dx.doi.org/10.1007/s00259-021-05262-xDOI Listing
May 2021

Consensus on molecular imaging and theranostics in neuroendocrine neoplasms.

Eur J Cancer 2021 Mar 12;146:56-73. Epub 2021 Feb 12.

Department of Nuclear Medicine, Universitätsklinikum, Essen, Germany. Electronic address:

Nuclear medicine plays an increasingly important role in the management neuroendocrine neoplasms (NEN). Somatostatin analogue (SSA)-based positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT) have been used in clinical trials and approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). European Association of Nuclear Medicine (EANM) Focus 3 performed a multidisciplinary Delphi process to deliver a balanced perspective on molecular imaging and radionuclide therapy in well-differentiated neuroendocrine tumours (NETs). NETs form in cells that interact with the nervous system or in glands that produce hormones. These cells, called neuroendocrine cells, can be found throughout the body, but NETs are most often found in the abdomen, especially in the gastrointestinal tract. These tumours may also be found in the lungs, pancreas and adrenal glands. In addition to being rare, NETs are also complex and may be difficult to diagnose. Most NETs are non-functioning; however, a minority present with symptoms related to hypersecretion of bioactive compounds. NETs often do not cause symptoms early in the disease process. When diagnosed, substantial number of patients are already found to have metastatic disease. Several societies' guidelines address Neuroendocrine neoplasms (NENs) management; however, many issues are still debated, due to both the difficulty in acquiring strong clinical evidence in a rare and heterogeneous disease and the different availability of diagnostic and therapeutic options across countries. EANM Focus 3 reached consensus on employing gallium-labelled somatostatin analogue ([Ga]Ga-DOTA-SSA)-based PET/CT with diagnostic CT or magnetic resonance imaging (MRI) for unknown primary NET detection, metastatic NET, NET staging/restaging, suspected extra-adrenal pheochromocytoma/paraganglioma and suspected paraganglioma. Consensus was reached on employing fluorine-fluoro-2-deoxyglucose ([F]FDG) PET/CT in neuroendocrine carcinoma, G3 NET and in G1-2 NET with mismatched lesions (CT-positive/[Ga]Ga-DOTA-SSA-negative). Peptide receptor radionuclide therapy (PRRT) was recommended for second line treatment for gastrointestinal NET with [Ga]Ga-DOTA-SSA uptake in all lesions, in G1/G2 NET at disease progression, and in a subset of G3 NET provided all lesions are positive at [F]FDG and [Ga]Ga-DOTA-SSA. PRRT rechallenge may be used for in patients with stable disease for at least 1 year after therapy completion. An international consensus is not only a prelude to a more standardised management across countries but also serves as a guide for the direction to follow when designing new research studies.
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http://dx.doi.org/10.1016/j.ejca.2021.01.008DOI Listing
March 2021

The Safety and Efficacy of the Repeated PRRT with [Y]Y/[Lu]Lu-DOTATATE in Patients with NET.

Int J Endocrinol 2021 23;2021:6615511. Epub 2021 Jan 23.

Nuclear Medicine Department, Medical University of Warsaw, Warsaw, Poland.

Purpose: The peptide receptor radionuclide therapy (PRRT) is a treatment option for patients with disseminated, inoperable G1 and G2 neuroendocrine tumours (NETs). The study aims to evaluate the safety, efficacy, and progression-free survival (PFS) of patients after retreatment (R-PRRT) and re-retreatment (RR-PRRT) with tandem isotopes [Y]Y/[Lu]Lu-DOTATATE. . Out of 99 treated patients with G1 and G2 NETs, 26 were included in the study and treated with the repeated PRRT (with 5 undergoing the re-repeated PRRT treatment) after an initial positive response to four PRRT cycles and later progression of the disease. [Ga]Ga-DOTATATE PET/CT and CT/MRI procedures were performed before and after the treatment. Patients were treated with [Y]Y/[Lu]Lu-DOTATATE (1 : 1) with mixed amino acid infusion for kidney protection. Toxicity was evaluated using the CTCAE 3.0 criteria.

Results: The median follow-up was 88 months (the range: 42-164). The median cumulative administered activity was 22.2 GBq (the range: 17.8-30.7 GBq). Myelodysplastic syndrome occurred in one patient (3.8%), and grade 4 renal toxicity was also detected in one patient (3.8%). No other cases of grade 3 or 4 bone marrow and renal toxicity were observed. The median PFS rate was 31 months after the PRRT and 23 months following the R-PRRT. The OS rate from the diagnosis (OS-d) was 109 months and from the start of the PRRT (OS-t)-92.4 months. During the restaging, 3-6 months after the PRRT, PR, SD, and PD were observed in 19.2%, 80.8%, and 0% of the patients, respectively. After the R-PRRT, PR, SD, and PD were observed in 50%, 42.3%, and 7.7% of the patients, respectively.

Conclusions: The repeated therapy with [Y]Y/[Lu]Lu-DOTATATE is safe and effective for patients with disseminated, inoperable G1 and G2 neuroendocrine tumours.
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http://dx.doi.org/10.1155/2021/6615511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847334PMC
January 2021

Parathyroid imaging with [99mTc]Tc-MIBI SPECT/CT - unexpected findings of bone marrow involvement of non-Hodgkin's lymphoma.

Endokrynol Pol 2020 ;71(3):271-272

Department of Nuclear Medicine, Medical University of Warsaw, Warsaw, Poland.

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http://dx.doi.org/10.5603/EP.a2020.0023DOI Listing
January 2020

[ Ga]Ga-Prostate-Specific Membrane Antigen PET/CT: a novel method for imaging patients with hepatocellular carcinoma.

Eur J Nucl Med Mol Imaging 2021 Mar 3;48(3):883-892. Epub 2020 Sep 3.

Nuclear Medicine Department, Medical University of Warsaw, ul. Banacha 1 a, 02-097, Warsaw, Poland.

Purpose: Prostate-specific membrane antigen (PSMA) is not only highly expressed on the surface prostate cancer cells but is also elevated during angiogenesis in other cancer cell types, including hepatocellular carcinoma (HCC). This study aimed to evaluate the feasibility of using PET/CT imaging with [Ga]Ga-PSMA-11 in HCC and its impact on patient management.

Methods: Fifteen patients (13 men and two women; aged 55.6 ± 18.2 years) with HCC were enrolled in this prospective, single-institution study. All patients underwent contrast-enhanced MRI/CT, [Ga]Ga-PSMA-11 PET/CT, and histopathological verification of lesions.

Results: No radiopharmaceutical-related adverse events were noted. Visual interpretation showed increased accumulation of [Ga]Ga-PSMA-11 in all HCC patients. The tumor-to-liver ratio (TLR) was 3.6 ± 2.1, and the maximal standardized uptake value (SUV) was 13.5 ± 7.1. There were no significant differences in the SUVs or TLR between newly diagnosed and recurrent patients. No statistically significant relationship was found between serum concentration of tumor markers (i.e., AFP, CA 19-9, CEA) and PET parameters. Results of the [Ga]Ga-PSMA-11 PET/CT changed the treatment strategy in five (33%) patients. PSMA staining showed visible heterogeneity in terms of intensity and distribution: the reaction was weak and only observed in a few vessels in pseudoglandular patterns of HCC, while it was homogeneously strong, with some hot spots, in trabecular patterns of HCC.

Conclusion: [Ga]Ga-PSMA-11 PET/CT can detect PSMA expression in vivo in patients with HCC and is useful for guiding treatment strategies. Further investigation of the clinical utility of this method in HCC is warranted.
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http://dx.doi.org/10.1007/s00259-020-05017-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036201PMC
March 2021

Peptide Receptor Radionuclide Therapy During the COVID-19 Pandemic: Are There Any Concerns?

J Nucl Med 2020 Aug 23;61(8):1094-1095. Epub 2020 Jun 23.

Department of Nuclear Medicine, University Hospital Essen, Essen, Germany, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California.

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http://dx.doi.org/10.2967/jnumed.120.249136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413236PMC
August 2020

Teaching nuclear medicine in the pandemic-a new challenge for the faculty.

Eur J Nucl Med Mol Imaging 2020 08 20;47(9):2075-2077. Epub 2020 May 20.

Department of Nuclear Medicine, Medical University of Warsaw, Warsaw, Poland.

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http://dx.doi.org/10.1007/s00259-020-04865-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237224PMC
August 2020

Effect of peptide receptor radionuclide therapy (PRRT) with tandem isotopes - [90Y]Y/[177Lu]Lu-DOTATATE in patients with disseminated neuroendocrine tumours depending on [18F]FDG PET/CT qualification in Polish multicentre experience - do we need [18F]FDG PET/CT for qualification to PRRT?

Endokrynol Pol 2020 15;71(3):240-248. Epub 2020 Apr 15.

Nuclear Medicine Department, Medical University of Warsaw, Poland.

Introduction: Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues is a treatment option for patients with disseminated neuroendocrine tumours (NET). The aim of the study was the evaluation of the role of [¹⁸F]FDG PET/CT in predicting response, progression-free survival (PFS) and overall survival (OS) after tandem therapy [⁹⁰Y]Y/[¹⁷⁷Lu]Lu-DOTATATE.

Material And Methods: Seventy-five patients with histopathologically proven NET G1 and G2 were included in the study. Before treatment [⁶⁸Ga]Ga-DOTATATE PET/CT and [¹⁸F]FDG PET/CT was performed. Patients were treated with [⁹⁰Y]Y/[¹⁷⁷Lu]Lu-DOTATATE (1:1) with mixed amino-acid infusion for kidney protection.

Results: Progression-free survival was 22.2 months for [¹⁸F]FDG-positive patients and 59.3 months for [¹⁸F]FDG-negative patients (p = 0.003). The OS from diagnosis (OS-D) and from the start of PRRT (OS-T) was not reached in [¹⁸F]FDG-negative patients, and in [¹⁸F]FDG-positive patients it was 71.8 months and 55.8 months, respectively. The observed overall one-year survival in [¹⁸F]FDG-positive vs. [¹⁸F]FDG-negative patients was 96.8% vs. 99.1%, two-year survival was 88.9% vs. 96%, and five-year survival was 58.8% vs. 88%, respectively. The one-year and two-year risk of progression was 15%vs. 58.9% in [¹⁸F]FDG-positive patients and 11% vs. 32% in [18F]FDG-negative patients. The objective response rate (ORR) [¹⁸F]FDG-positive vs. [¹⁸F]FDG-negative patients was 41.7% vs. 17%.

Conclusions: [¹⁸F]FDG-positive patients have statistically significant shorter survival parameters than [¹⁸F]FDG-negative patients. The risk of progression in [¹⁸F]FDG-positive vs. [¹⁸F]FDG-negative patients in one-year follow-up is comparable, whereas in two-year follow-up it is nearly two times higher for [¹⁸F]FDG PET/CT-positive patients.
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http://dx.doi.org/10.5603/EP.a2020.0014DOI Listing
April 2020

Targeted α-Emitter Therapy of Neuroendocrine Tumors.

Semin Nucl Med 2020 Mar;50(2):171-176

Nuclear Medicine Department, Medical University of Warsaw, Poland.

Neuroendocrine tumors (NET) are a heterogeneous group of neoplasms, arising from cells of the endocrine system, with various clinical behaviors. Although these neoplasms are considered rare, a significant increase in the incidence and detectability of NET has been noted in many epidemiological studies in recent years. Among the various therapeutic options, peptide receptor radionuclide therapy (PRRT), using somatostatine has been shown to be highly effective and a well-tolerated therapy, improving survival parameters. The current use of radionuclides for PRRT is β-emitters. Due to hypoxia cancer tissue could be resistant for β-emitters. Quite long penetration range had a significant impact on side effects. α-particles with higher energy and shorter penetration range in comparison to β-particles, have distinct advantages for use in targeted therapy. The clinical experience with somatostatine based targeted α therapy (TAT) in NET showed very promising results even in patienicts refractory to treatment with β-emitters. This article summarizes current developments in preclinical and clinical investigation on TAT in NET.
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http://dx.doi.org/10.1053/j.semnuclmed.2019.11.003DOI Listing
March 2020

Ac- and Bi-Substance P Analogues for Glioma Therapy.

Semin Nucl Med 2020 Mar;50(2):141-151

Department of Neurosurgery, Bern and University of Basel, Switzerland.

Within the last decades, there has been no major improvement in treatment of patients with glioma, especially with glioblastoma multiforme (GBM) which is related to specific features of this tumor type, such as heterogeneity at the macroscopic, microscopic and genetic level, the infiltrative nature of tumors and the obstacle of the brain-blood barrier which limits the accessability of most drugs. The current standard of care is surgical resection, followed by radio- and chemotherapy. After first-line treatment of the primary lesion, tumor recurrence is diagnosed in virtually all GBM patients. Treatment of tumor recurrence represents a challenging clinical task. Surgical resection to relief symptoms of mass effect and/or salvage chemotherapy are often considered as last therapeutic option. A new treatment option is urgently needed. Targeted alpha therapy with an intratumoral injection of Bi-DOTA-Substance P (SP) or Ac-DOTAGA-Substance P has been introduced into the therapeutic armamentarium of recurrent GBM. There are many advantages of using SP such as very high prevalence of increased NK-1 expression in GBM cells, regardless of the degree of malignancy, and expression of the NK-1 receptor system not only on the membrane of cancer cells but also strong expression of NK1 receptors within the tumor neovasculature suggesting concomitant targeting of vascular and neoplastic structures. Radioisotopes with different physical properties, mainly beta-emitting metallic radionuclides, were implemented for brain tumor treatment. Based on their radiophysical properties, however, alpha emitters exhibit more promising properties. In investigator-initiated phase I and II studies, targeted alpha therapy using Bi-213/Ac-225 radiolabeled Substance P for malignant gliomas compare favorably with standard therapy, with the limitation that no large controlled series have so far been generated. Further development should focus on the improvement of the biological and chemical properties of the compound and the application by dedicated catheter systems to improve the intratumoral distribution of the radiopharmaceutical within growth and infiltrative zone of these glial neoplasms.
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http://dx.doi.org/10.1053/j.semnuclmed.2019.11.004DOI Listing
March 2020

Sequential delayed [18 F]FDG PET/CT examinations in the pharynx.

Sci Rep 2020 02 19;10(1):2910. Epub 2020 Feb 19.

Nuclear Medicine Department, Greater Poland Cancer Centre, Garbary 15, 61-866, Poznan, Poland.

This study aimed to evaluate the usefulness of the biphasic 2-deoxy-2-[18 F]fluoro-D-glucose positron emission tomography/computed tomography ([18 F]FDG PET/CT) examinations in terms of distinguishing benign and malignant lesions within the pharynx. 139 patients underwent sequential biphasic [18 F]FDG PET/CT examinations at 60 and 90 minutes (min) post intravenous injection (p.i.) of the [18 F]FDG. We evaluated the metabolic activity of 93 malignant lesions and 59 benign findings within pharynx as well as 70 normal blood vessels. We evaluated the maximal and mean standardized uptake value (SUVmax, SUVmean) and the retention index (RI-SUVmax). We used the receiver operating characteristics (ROC) analysis to obtain the prognostic metabolic indices cut-off which may differentiate between benign and malignant lesions. The SUVmax value cut-off at 60 and 90 min p.i. differentiating between normal and abnormal metabolic activity in the pharynx was 1.9 and 2.0, respectively. When compared benign and malignant lesions, the SUVmax on initial and delayed scans were 3.1 and 3.6, respectively. In this material, the increase of the SUVmax value over time of 1.7% suggested abnormality, while RI-SUVmax of 5.7% indicated malignant etiology. The biphasic [18 F]FDG PET/CT study protocol is useful in better stratification of normal and abnormal glucose metabolism activity in the pharynx.
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http://dx.doi.org/10.1038/s41598-020-59832-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031226PMC
February 2020

68Ga-PSMA PET/CT in Recurrence Prostate Cancer. Should We Perform Delayed Image in Cases of Negative 60 Minutes Postinjection Examination?

Clin Nucl Med 2020 Apr;45(4):e213-e214

From the Department of Nuclear Medicine, Medical University of Warsaw, Warsaw, Poland.

We report a case of a 59-year-old man with prostate adenocarcinoma, Gleason score 9 after prostatectomy and adjuvant radiotherapy. The patient showed biochemical recurrence. On standard Ga-PSMA PET/CT examination, 60 minutes postinjection, the PET/CT images showed only trace accumulation in the ureters. To identify lesions close to the ureters, imaging of the pelvis was performed 2 hours postinjection. The delayed image showed clearly visible increased uptake in a right internal iliac lymph node that was normal-sized by CT. The patient underwent radiotherapy with planning based on the Ga-PSMA PET/CT image. Follow-up testing showed prostate-specific antigen level reduction to 0.04 ng/mL.
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http://dx.doi.org/10.1097/RLU.0000000000002966DOI Listing
April 2020

Tumor uptake in glioblastoma multiforme after IV injection of [Lu]Lu-PSMA-617.

Eur J Nucl Med Mol Imaging 2020 06 10;47(6):1605-1606. Epub 2020 Feb 10.

Department of Nuclear Medicine, Medical University of Warsaw, ul. Banacha 1 a, 02-097, Warsaw, Poland.

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http://dx.doi.org/10.1007/s00259-020-04715-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188710PMC
June 2020

Tandem peptide receptor radionuclide therapy using Y/Lu-DOTATATE for neuroendocrine tumors efficacy and side-effects - polish multicenter experience.

Eur J Nucl Med Mol Imaging 2020 04 24;47(4):922-933. Epub 2020 Jan 24.

Nuclear Medicine Department, Medical University of Warsaw, ul. Banacha 1 a, 02-097, Warsaw, Poland.

Introduction: One of the concepts of theranostics in nuclear medicine is peptide receptor radionuclide therapy (PRRT), whereby labeled somatostatin analogs are used for imaging and treating inoperable or disseminated neuroendocrine tumors (NET).

Aim: The aim of the study was to determine the therapeutic efficacy and toxicity of tandem Y /Lu-DOTATATE in patients with disseminated NET in a multicenter trial.

Materials And Methods: 103 patients with NET G1/G2 treated with Y/Lu-DOTATATE (1:1) with amino-acid infusion for nephroprotection were included in the study.

Results: Overall survival from the disease diagnosis (OS-D) was 127.4 months and from the time of PRRT (OS-T) was 89.5 months. Progression-free survival (PFS) was 29.9 months. An analysis based on the proliferation index revealed a statistically significant impact on PFS and OS-T (PFS G1 vs G2, 59.3 vs 24.3 months; OS-T G1 vs G2, not reached vs 79.9 months). The effect of the primary disease site was also analyzed. For pancreatic vs small bowel vs large bowel, the PFS was 30.8 vs 30.3 vs 40.6 months, the OS-T was 94 vs 61.9 vs 131.2 months and OS-D was 130.4 vs 89.2 vs not reached months, respectively. The 2-year risk of progression was 42%. The probability of 2-year and 5-year overall survival was 89% and 62%, respectively. PRRT was well tolerated by all patients. One patient (1%) developed myelodysplastic syndrome. No other grade 3 and 4 hematological or renal toxicity was observed.

Conclusions: This multicenter trial showed that tandem Y/Lu-DOTATATE is highly effective and safe therapy for patients with disseminated NET.
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http://dx.doi.org/10.1007/s00259-020-04690-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075861PMC
April 2020

Liver transplantation as an option of treatment for a giant primary hepatic neuroendocrine tumour.

Endokrynol Pol 2019 ;70(6):520-521

Department of General, Vascular and Transplant Surgery, Medical University of Silesia, Katowice, Poland.

There are no clear guidelines for the treatment of hepatic neuroendocrine tumours. Surgical resections - though rarely radical - seem to be the treatment of choice. Thermoablation, chemoembolisation, or cytoreductive surgery of hepatic focal lesions are often recommended. Pharmacological treatment is based on somatostatin analogues. Liver transplantation is available for a strictly selected group of patients with hepatic neuroendocrine tumours [5]. In the case described above, there were a number of factors that affected the decision about eligibility: first of all - very slow growth of the tumour, its size, and typical multifocality, which made it impossible to perform resection, lack of neoplastic focus outside the liver, and low Ki-67 proliferation index of ≤ 2%. The surgical risk was escalated due to the giant tumour mass and the laparotomy, which was performed twice.
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http://dx.doi.org/10.5603/EP.a2019.0052DOI Listing
May 2020

Correction to: Glioblastoma multiforme: another potential application for Ga-PSMA PET/CT as a guide for targeted therapy.

Eur J Nucl Med Mol Imaging 2020 Feb;47(2):514

Department of Nuclear Medicine, Medical University of Warsaw, Banacha 1 a, 02-097, Warsaw, Poland.

The author names of the original version of this article were inadvertently interchanged. Correct author names are presented here.
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http://dx.doi.org/10.1007/s00259-019-04560-9DOI Listing
February 2020

68Ga-Prostate-Specific Membrane Antigen-11 PET/CT: A New Imaging Option for Recurrent Glioblastoma Multiforme?

Clin Nucl Med 2020 Jan;45(1):11-18

From the Nuclear Medicine Department, Medical University of Warsaw, Poland.

Background: Glioblastoma multiforme (GBM) is the most common and most aggressive primary tumor of the brain. After initial therapy and total resection of GBM, 80% to 90% of recurrences occur at the surgical margins. Currently, limited data are available in the literature on the possible use of Ga-prostate-specific membrane antigen (PSMA-11) for diagnosis of recurrence in GBM patients. The aim was to assess the feasibility and potential of Ga-PSMA-11 PET/CT as a diagnostic procedure in patients with histologically confirmed of GBM and suspected recurrent disease on MRI.

Results: No radiopharmaceutical-related adverse events were noted. Characterization of recurrent disease with MRI included T2-weighted fast spin-echo images, fluid-attenuated inversion recovery and diffusion-weighted imaging sequences, and gadolinium enhanced T1-weighted images. Visual interpretation of PET showed increased accumulation of Ga-PSMA-11 in recurrent lesion detected by T1 contrast enhanced and diffusion-weighted imaging images in all patients with a median SUVmax of the tumor of 6.5 and an SUVmean of 3.5. The median tumor-to-background brain ratio and tumor-to-liver ratio obtained from Ga-PSMA-11 PET/CT were 96.7 and 0.8, respectively.

Conclusions: The extremely low background uptake in normal brain tissue and consequently high tumor-to-brain ratio make Ga-PSMA-11 PET/CT highly promising for diagnosis of recurrent disease in GBM patients. Although PSMA expression in recurrent GBM also opens a potential way for targeted peptide therapy with α/β-emitters as well as for prediction of treatment with antiangiogenic agents, the low tumor-to-liver ratio observed in the majority of patients in this study suggests a limited role of radiolabeled PSMA ligands for targeted radionuclide therapy of recurrent GBM.
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http://dx.doi.org/10.1097/RLU.0000000000002806DOI Listing
January 2020

Safety and efficacy of targeted alpha therapy with Bi-DOTA-substance P in recurrent glioblastoma.

Eur J Nucl Med Mol Imaging 2019 03 29;46(3):614-622. Epub 2018 Nov 29.

European Commission, Joint Research Centre, Directorate for Nuclear Safety and Security, Karlsruhe, Germany.

Treatment options for recurrent glioblastoma multiforme (GBM) are very limited. GBM cells express high levels of the GPCR neurokinin type 1 receptor (NK-1R), and a modified substance P can be used as its ligand for the tumor cell targeting. Targeted alpha therapy with DOTA-Substance P labeled with the short range alpha emitter Bi allows for selective irradiation and killing of tumor cells.

Material And Methods: Twenty patients with recurrent GBM were included into the study following a standard therapy. 1-2 intracavitary or intratumoral port-a-cath systems were stereotactically inserted. Patients were treated with 1-7 doses of Bi-DOTA-Substance P (Bi-DOTA-SP) in 2-month intervals. Ga-DOTA-Substance P (Ga-DOTA-SP) was co-injected with Bi-DOTA-SP to assess the biodistribution using PET/CT. Therapeutic response was monitored with performance status and MRI imaging.

Results: Treatment with activity up to 11.2 GBq Bi-DOTA-SP was well tolerated with only mild and transient adverse reactions. The median progression free survival was 2.7 months. The median overall survival from the first diagnosis was 23.6 months and median survival after recurrence was 10.9 months. The median survival time from the start of Bi-DOTA-SP was 7.5 months.

Conclusions: Treatment of recurrent GBM with Bi-DOTA-SP is safe and well tolerated. The median overall survival after recurrence of 10.9 months compares favorably to the available alternative treatment options. Once the supply of high activity Ac/Bi radionuclide generators is secured, targeted alpha therapy with Bi-DOTA-SP may evolve as a promising novel option to treat recurrent GBM.
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http://dx.doi.org/10.1007/s00259-018-4225-7DOI Listing
March 2019

Simultaneous breast cancer and DLBCL lymphoma - role of PET/CT examination with 18F-FDG and 18F-FES.

Nucl Med Rev Cent East Eur 2018 29;21(2):113-114. Epub 2018 Jun 29.

Zakład Medycyny Nuklearmej z Ośrodkiem PET Świętokrzyskie Centrum Onkologii, Artwińskiego 3, 25-734 Kielce.

Breast cancer is the most common cancer in women in the western world. The estrogen receptor (ER) is expressed in two thirds of newly diagnosed breast cancers, so hormonal treatment is performed only in the receptor positive patients. The most successful ER imaging radiopharmaceutical in PET techniques is 16α-[18F]-flouro-17β-estradiol (¹⁸F-FES). The diffuse large B cell lymphoma (DLBCL) is one of the most common NHL, however, non-Hodgkin lymphoma constitutes only 4% of all primary cancers in women. The typical staging of disease is done using 18-fluorodeoksyglukose (¹⁸F-FDG) PET/CT.
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http://dx.doi.org/10.5603/NMR.a2018.0020DOI Listing
October 2018

TeleNEN as a telemedicine model for neuroendocrine neoplasm management in case of Meckel's diverticulum NET.

Endokrynol Pol 2018 ;69(3):313-317

Nuclear Medicine Department, Medical University of Warsaw, Warsaw, Poland.

A case of 25- years-old female with NET deriving from Meckel's diverticulum is described. The patient had one year history of dermatological skin problems. Ultrasound examination of abdomen performed because of arterial hypertension, revealed multiple hepatic lesions, which was confirmed in contrast enhanced CT. The typical contrast enhanced metastatic lesions in CT and elevated levels of chromogranin A suggested NET of unknown origin. SRS with 99mTc-HYNICTOC was perform for primary tumor localization, and revealed liver and paraaortic lymph nodes metastases, but no sign of primary tumor location. As a next step for primary tumor localization 68Ga-DOTATATE PET/CT was done, which revealed focus of increased uptake in small intestine considered to be the primary tumor site. The imaging and clinical history of patient was discussed on ENETS Tumor Board. Due to location of primary tumor in the small intestine with no anatomical changes in CT, laparotomy guided with gamma probe after 68Ga-DOTATATE injection was performed. During surgery procedure, the primary tumor was hardly palpable in the tip of Meckel's diverticulum, confirmed by gamma probe. After surgery, tandem peptide receptor radionuclide therapy (PRRT) was started. Patient received 4 doses of 90Y/177Lu-DOTATATE with total activity of 360 mCi (13.32 GBq). The three months follow up 68Ga-DOTATATE PET/CT had shown stable disease of patient. The presented case showed importance role of multidisciplinary team cooperation in patient management. Use of RGS is essential in cases like presented, when the tumor cannot be localized only by surgical palpation.
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http://dx.doi.org/10.5603/EP.2018.0033DOI Listing
October 2018

Prolonged survival in secondary glioblastoma following local injection of targeted alpha therapy with Bi-substance P analogue.

Eur J Nucl Med Mol Imaging 2018 07 30;45(9):1636-1644. Epub 2018 Apr 30.

European Commission, Joint Research Centre, Directorate for Nuclear Safety and Security, Karlsruhe, Germany.

Background: Glioblastoma multiforme (GBM), the most common malignant brain tumor, mainly manifests as a primary de novo and less frequently as a secondary glial neoplasm. GBM has been demonstrated to overexpress the NK-1 receptor and substance P can be used as a ligand for targeted therapy. Alpha emitters, e.g. Bi, that deposit their high energy within a short range allow the selective irradiation of tumor cells while sparing adjacent neuronal structures.

Material And Methods: Among 50 glioma patients of different subtypes that have to date been treated with targeted alpha therapy at the Medical University Warsaw, we report here the data on nine patients with secondary GBM. Following surgery, chemo- and radiotherapy, recurrent GBM was treated by intracavitary injection of 1-6 doses of 0.9-2.3 GBq Bi- DOTA-[Thi,Met(O)]-substance P (Bi-DOTA-SP) in 2-month intervals. Ga-DOTA-[Thi,Met(O)]-substance P (Ga-DOTA-SP) was co-injected with the therapeutic doses to assess biodistribution using PET/CT. Therapeutic response was monitored with MRI.

Results: Treatment with activities ranging from 1.4 to 9.7 (median 5.8) GBq Bi- DOTA-SP was well tolerated with only mild transient adverse reactions, mainly headaches due to a transient perfocal edema reaction. The median progression free survival and overall survival time following the initiation of alpha therapy was 5.8 and 16.4 months, respectively. The median overall survival time from the first diagnosis was 52.3 months. Two out of nine patients are still alive 39 and 51 months, respectively, after the initiation of the therapy.

Conclusions: Targeted alpha therapy of secondary GBM with Bi-DOTA-SP is safe and well tolerated and may evolve as a promising novel therapeutic option for secondary GBM.
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http://dx.doi.org/10.1007/s00259-018-4015-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061489PMC
July 2018

Glioblastoma multiforme: another potential application for Ga-PSMA PET/CT as a guide for targeted therapy.

Eur J Nucl Med Mol Imaging 2018 05 31;45(5):886-887. Epub 2018 Jan 31.

Department of Nuclear Medicine, Medical University of Warsaw, ul. Banacha 1 a, 02-097, Warsaw, Poland.

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http://dx.doi.org/10.1007/s00259-018-3934-2DOI Listing
May 2018

Correction to: Dosimetry in clinical radionuclide therapy: the devil is in the detail.

Eur J Nucl Med Mol Imaging 2018 04;45(4):676

European Association of Nuclear Medicine, Board, Vienna, Austria.

The above article which was published in Volume 44/ Issue 12 has incorrect page numbers. Instead of 1-3, it should have been 2137-2139.
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http://dx.doi.org/10.1007/s00259-017-3921-zDOI Listing
April 2018

Optimizing Somatostatin Receptor Imaging in Patients With Neuroendocrine Tumors: The Impact of 99mTc-HYNICTOC SPECT/SPECT/CT Versus 68Ga-DOTATATE PET/CT Upon Clinical Management.

Clin Nucl Med 2017 Dec;42(12):905-911

From the *Department of Nuclear Medicine, Medical University of Warsaw, Warsaw, Poland; and †Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.

Aim: The presence of somatostatin receptors in neuroendocrine tumors allows visualization with radiolabeled somatostatin analogs in vivo. The aim of this prospective study was to compare somatostatin receptor imaging using Tc-HYNICTOC with Ga-DOTATATE (DOTA-DPhe1,Tyr3-octreotate) with respect to sensitivity, specificity, and impact upon clinical decision making.

Methods: Sixty-eight patients (30 men, 38 women; aged 56.4 ± 13.5 years) with disseminated, histologically proven neuroendocrine tumor were enrolled. All patients with previous Tc-HYNICTOC (Tektrotyd; POLATOM, Otwock, Poland) underwent Ga-DOTATATE PET/CT. Both examinations were compared on a per-patient and per-lesion basis.

Results: The sensitivity, specificity, positive and negative predictive values, and accuracy of Ga-DOTATATE and Tc-HYNICTOC were 100% versus 82%, 85% versus 69%, 97% versus 92%, 100% versus 47%, and 97% versus 79%, respectively.Concordant results were observed in 58 patients (49/68 positive on both Ga-DOTATATE and Tc-HYNICTOC and 9/68 negative in both examinations). Ten of 68 patients had Ga-DOTATATE-positive, Tc-HYNICTOC-negative studies. Two hundred eighteen lesions were detected using Tc-HYNICTOC, compared with 546 lesions using Ga-DOTATATE (P < 0.0001). Ga-DOTATATE detected a higher number of lesions in bone and lymph nodes, liver, intestine, and pancreas and had a higher sensitivity for subcentimeter abnormalities than Tc-HYNICTOC. Ga-DOTATATE led to management change in 23 (34%) of 68 patients.

Conclusions: Ga-DOTATATE has a higher sensitivity than Tc-HYNICTOC for the detection of neuroendocrine tumors. Ga-DOTATATE proved superior to Tc-HYNICTOC in detecting subcentimeter skeletal, lymph node, and liver metastases. Ga-DOTATATE PET/CT changed clinical decision making in one third of patients.
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http://dx.doi.org/10.1097/RLU.0000000000001877DOI Listing
December 2017

Dosimetry in clinical radionuclide therapy: the devil is in the detail.

Eur J Nucl Med Mol Imaging 2017 11 10;44(12):2137-9. Epub 2017 Sep 10.

European Association of Nuclear Medicine, Board, Vienna, Austria.

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http://dx.doi.org/10.1007/s00259-017-3820-3DOI Listing
November 2017

Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours).

Endokrynol Pol 2017 ;68(2):79-110

Klinika Endokrynologii i Nowotworów Neuroendokrynnych, Katedra Patofizjologii i Endokrynologii, Śląski Uniwersytet Medyczny.

Progress in the diagnostics and therapy of gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NEN), the published results of new randomised clinical trials, and the new guidelines issued by the European Neuroendocrine Tumour Society (ENETS) have led the Polish Network of Neuroendocrine Tumours to update the 2013 guidelines regarding management of these neoplasms. We present the general recommendations for the management of NENs, developed by experts during the Third Round Table Conference - Diagnostics and therapy of gastro-entero-pancreatic neuroendocrine neoplasms: Polish recommendations in view of current European recommenda-tions, which took place in December 2016 in Żelechów near Warsaw. Drawing from the extensive experience of centres dealing with this type of neoplasms, we hope that we have managed to develop the optimal management system, applying the most recent achievements in the field of medicine, for these patients, and that it can be implemented effectively in Poland. These management guidelines have been arranged in the following order: gastric and duodenal NENs (including gastrinoma); pancreatic NENs; NENs of the small intestine and appendix, and colorectal NENs.
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http://dx.doi.org/10.5603/EP.2017.0015DOI Listing
July 2017