Development and Evaluation of the Magnetic Properties of a New Manganese (II) Complex: A Potential MRI Contrast Agent.

Magnetic resonance imaging (MRI) is a non-invasive powerful modern clinical technique that is extensively used for the high-resolution imaging of soft tissues. To obtain high-definition pictures of tissues or of the whole organism this technique is enhanced by the use of contrast agents. Gadolinium-based contrast agents have an excellent safety profile. However, over the last two decades, some specific concerns have surfaced. Mn(II) has different favorable physicochemical characteristics and a good toxicity profile, which makes it a good alternative to the Gd(III)-based MRI contrast agents currently used in clinics. Mn(II)-disubstituted symmetrical complexes containing dithiocarbamates ligands were prepared under a nitrogen atmosphere. The magnetic measurements on Mn complexes were carried out with MRI phantom measurements at 1.5 T with a clinical magnetic resonance. Relaxivity values, contrast, and stability were evaluated by appropriate sequences. Studies conducted to evaluate the properties of paramagnetic imaging in water using a clinical magnetic resonance showed that the contrast, produced by the complex [Mn(II)(L')2] × 2H2O (L' = 1.4-dioxa-8-azaspiro[4.5]decane-8-carbodithioate), is comparable to that produced by gadolinium complexes currently used in medicine as a paramagnetic contrast agent.

Technetium-99m Radiopharmaceuticals for Ideal Myocardial Perfusion Imaging: Lost and Found Opportunities.

The favorable nuclear properties in combination with the rich coordination chemistry make technetium-99m the radioisotope of choice for the development of myocardial perfusion tracers. In the early 1980s, [99mTc]Tc-Sestamibi, [99mTc]Tc-Tetrofosmin, and [99mTc]Tc-Teboroxime were approved as commercial radiopharmaceuticals for myocardial perfusion imaging in nuclear cardiology. Despite its peculiar properties, the clinical use of [99mTc]Tc-Teboroxime was quickly abandoned due to its rapid myocardial washout. Despite their widespread clinical applications, both [99mTc]Tc-Sestamibi and [99mTc]Tc-Tetrofosmin do not meet the requirements of an ideal perfusion imaging agent due to their relatively low first-pass extraction fraction and high liver absorption. An ideal radiotracer for myocardial perfusion imaging should have a high myocardial uptake; a high and stable target-to-background ratio with low uptake in the lungs, liver, stomach during the image acquisition period; a high first-pass myocardial extraction fraction and very rapid blood clearance; and a linear relationship between radiotracer myocardial uptake and coronary blood flow. Although it is difficult to reconcile all these properties in a single tracer, scientific research in the field has always channeled its efforts in the development of molecules that are able to meet the characteristics of ideality as much as possible. This short review summarizes the developments in 99mTc myocardial perfusion tracers, which are able to fulfill hitherto unmet medical needs and serve a large population of patients with heart disease, and underlines their strengths and weaknesses, the lost and found opportunities thanks to the developments of the new ultrafast SPECT technologies.

Rhenium Radioisotopes for Medicine, a Focus on Production and Applications.

In recent decades, the use of alpha; pure beta; or beta/gamma emitters in oncology, endocrinology, and interventional cardiology rheumatology, has proved to be an important alternative to the most common therapeutic regimens. Among radionuclides used for therapy in nuclear medicine, two rhenium radioisotopes are of particular relevance: rhenium-186 and rhenium-188. The first is routinely produced in nuclear reactors by direct neutron activation of rhenium-186 via 185Re(n,γ)186Re nuclear reaction. Rhenium-188 is produced by the decay of the parent tungsten-188. Separation of rhenium-188 is mainly performed using a chromatographic 188W/188Re generator in which tungsten-188 is adsorbed on the alumina column, similar to the 99Mo/99mTc generator system, and the radionuclide eluted in saline solution. The application of rhenium-186 and rhenium-188 depends on their specific activity. Rhenium-186 is produced in low specific activity and is mainly used for labeling particles or diphosphonates for bone pain palliation. Whereas, rhenium-188 of high specific activity can be used for labeling peptides or bioactive molecules. One of the advantages of rhenium is its chemical similarity with technetium. So, diagnostic technetium analogs labeled with radiorhenium can be developed for therapeutic applications. Clinical trials promoting the use of 186/188Re-radiopharmaceuticals is, in particular, are discussed.

Highly Efficient Micro-Scale Liquid-Liquid In-Flow Extraction of 99mTc from Molybdenum.

The trend to achieve even more compact-sized systems is leading to the development of micro-scale reactors (lab-on-chip) in the field of radiochemical separation and radiopharmaceutical production. Technetium-99m extraction from both high and low specific activity molybdenum could be simply performed by MEK-driven solvent extraction if it were not for unpractical automation. The aim of this work is to develop a solvent extraction and separation process of technetium from molybdenum in a micro-scale in-flow chemistry regime with the aid of a capillary loop and a membrane-based separator, respectively. The developed system is able to extract and separate quantitatively and selectively (91.0 ± 1.8% decay corrected) the [99mTc]TcO4Na in about 20 min, by using a ZAIPUT separator device. In conclusion, we demonstrated for the first time in our knowledge the high efficiency of a MEK-based solvent extraction process of 99mTc from a molybdenum-based liquid phased in an in-flow micro-scale regime.

Synthesis and Characterization of Manganese Dithiocarbamate Complexes: New Evidence of Dioxygen Activation.

(1) Background: Metal dithiocarbamate compounds have long been the subject of research due to their ease of formation, excellent properties and potential applications. However, manganese complexes with dithiocarbamates, to our knowledge, have never been used for medical imaging applications. With the aim of developing a new class of mononuclear manganese(II)-based agents for molecular imaging applications, we performed a specific investigation into the synthesis of mononuclear bis-substituted Mn(II) complexes with dithiocarbamate ligands. (2) Methods: Synthesis in either open or inert atmosphere at different Mn(II) to diethyldithiocarbamate molar ratios were performed and the products characterized by IR, EA, ESI-MS and XRD analysis. (3) Results: We found that only under oxygen-free atmospheric conditions the Mn(II) complex MnL2, where L = diethyldithiocarbamate ligand, is obtained, which was further observed to react with dioxygen in the solid state to form the intermediate superoxo Mn(III) complex [MnL2(η2-O2)]. The existence of the superoxo complex was revealed by mass spectroscopy, and this species was interpreted as an intermediate step in the reaction that led the bis-substituted Mn(II) complex, MnL2, to transform into the tris-substituted Mn(III) complex, MnL3. A similar result was found with the ligand L' (= bis(N-ethoxyethyl)dithiocarbamate). (4) Conclusions: We found that in open atmosphere and in aqueous solution, only manganese(III) diethyldithiocarbamate complexes can be prepared. We report here a new example of a small-molecule Mn(II) complex that efficiently activates dioxygen in the solid state through the formation of an intermediate superoxide adduct.

Interdisciplinary Tasks in the Cyclotron Production of Radiometals for Medical Applications. The Case of 47Sc as Example.

The growing number of cyclotrons of different sizes installed in the territory has given a strong impulse to the production of conventional and emerging radionuclides for medical applications. In particular, the great advantage of using medical cyclotrons is the possibility to produce on-site, when needed (on-demand), with medical radionuclides of interest encouraging the personalized medicine approach. Radiometals satisfy the ideal characteristics that radionuclides should have for routine employment in nuclear medicine, especially since they have a robust chemistry suitable to synthetize stable in vivo radiopharmaceuticals with high radiochemical yields. In this letter several interdisciplinary aspects involved in the radiometals cyclotron production cycle are summarized focusing the attention on cyclotron production facilities, target material, and chemical processing available for medical applications. As an example, the current status and recent development in the production of the theranostic radionuclide scandium-47 have been reported.

Therapeutic Radiometals: Worldwide Scientific Literature Trend Analysis (2008⁻2018).

Academic journals have published a large number of papers in the therapeutic nuclear medicine (NM) research field in the last 10 years. Despite this, a literature analysis has never before been made to point out the research interest in therapeutic radionuclides (RNs). For this reason, the present study aims specifically to analyze the research output on therapeutic radiometals from 2008 to 2018, with intent to quantify and identify global trends in scientific literature and emphasize the interdisciplinary nature of this research field. The data search targeted conventional (131I, 90Y, 177Lu, 188Re, 186Re, 153Sm, 89Sr, 186Er) and emergent (67Cu, 47Sc, 223Ra, 166Ho, 161Tb, 149Tb, 212Pb/212Bi, 225Ac, 213Bi, 211At, 117mSn) RNs. Starting from this time frame, authors have analyzed and interpreted this scientific trend quantitatively first, and qualitatively after.

Perspectives on the Use of Liquid Extraction for Radioisotope Purification.

The reliable and efficient production of radioisotopes for diagnosis and therapy is becoming an increasingly important capability, due to their demonstrated utility in Nuclear Medicine applications. Starting from the first processes involving the separation of 99mTc from irradiated materials, several methods and concepts have been developed to selectively extract the radioisotopes of interest. Even though the initial methods were based on liquid-liquid extraction (LLE) approaches, the perceived difficulty in automating such processes has slowly moved the focus towards resin separation methods, whose basic chemical principles are often similar to the LLE ones in terms of chelators and phases. However, the emerging field of flow chemistry allows LLE to be easily automated and operated in a continuous manner, resulting in an even improved efficiency and reliability. In this contribution, we will outline the fundamentals of LLE processes and their translation into flow-based apparatuses; in addition, we will provide examples of radioisotope separations that have been achieved using LLE methods. This article is intended to offer insights about the future potential of LLE to purify medically relevant radioisotopes.

Correction: Uccelli, L., et al. Therapeutic Radiometals: Worldwide Scientific Literature Trend Analysis (2008⁻2018). Molecules 2019, 24, 640.

The authors wish to make the following corrections to their paper [...].

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

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.

68Ga-PSMA PET/CT in patients with recurrent prostate cancer after radical treatment: prospective results in 314 patients.

PURPOSE: We studied the usefulness of 68Ga-prostate-specific membrane antigen (PSMA) PET/CT for detecting relapse in a prospective series of patients with biochemical recurrence (BCR) of prostate cancer (PCa) after radical treatment. METHODS: Patients with BCR of PCa after radical surgery and/or radiotherapy with or without androgen-deprivation therapy were included in the study. 68Ga-PSMA PET/CT scans performed from the top of the head to the mid-thigh 60 min after intravenous injection of 150 ± 50 MBq of 68Ga-PSMA were interpreted by two nuclear medicine physicians. The results were correlated with prostate-specific antigen (PSA) levels at the time of the scan (PSApet), PSA doubling time, Gleason score, tumour stage, postsurgery tumour residue, time from primary therapy to BCR, and patient age. When available, 68Ga-PSMA PET/CT scans were compared with negative 18F-choline PET/CT scans routinely performed up to 1 month previously. RESULTS: From November 2015 to October 2017, 314 PCa patients with BCR were evaluated. Their median age was 70 years (range 44-92 years) and their median PSApet was 0.83 ng/ml (range 0.003-80.0 ng/ml). 68Ga-PSMA PET/CT was positive (one or more suspected PCa lesions detected) in 197 patients (62.7%). Lesions limited to the pelvis, i.e. the prostate/prostate bed and/or pelvic lymph nodes (LNs), were detected in 117 patients (59.4%). At least one distant lesion (LNs, bone, other organs, separately or combined with local lesions) was detected in 80 patients (40.6%). PSApet was higher in PET-positive than in PET-negative patients (P < 0.0001). Of 88 patients negative on choline PET/CT scans, 59 (67%) were positive on 68Ga-PSMA PET/CT. CONCLUSION: We confirmed the value of 68Ga-PSMA PET/CT in restaging PCa patients with BCR, highlighting its superior performance and safety compared with choline PET/CT. Higher PSApet was associated with a higher relapse detection rate.

Technetium Complexes and Radiopharmaceuticals with Scorpionate Ligands.

Scorpionate ligands have played a crucial role in the development of technetium chemistry and, recently, they have also fueled important advancements in the discovery of novel diagnostic imaging agents based on the γ-emitting radionuclide technetium-99m. The purpose of this short review is to provide an illustration of the most general and relevant results in this field, however without being concerned with the details of the analytical features of the various compounds. Thus, emphasis will be given to the description of the general features of technetium complexes with scorpionate ligands including coordination modes, structural properties and an elementary bonding description. Similarly, the most relevant examples of technetium-99m radiopharmaceuticals derived from scorpionate ligands and their potential interest for nuclear imaging will be summarized.

Influence of Storage Temperature on Radiochemical Purity of 99mTc-Radiopharmaceuticals.

The influence of effective room temperature on the radiochemical purity of 99mTc-radiopharmaceuticals was reported. This study was born from the observation that in the isolators used for the preparation of the 99mTc-radiopharmaceuticals the temperatures can be higher than those reported in the commercial illustrative leaflets of the kits. This is due, in particular, to the small size of the work area, the presence of instruments for heating, the continuous activation of air filtration, in addition to the fact that the environment of the isolator used for the 99mTc-radiopharmaceuticals preparation and storage is completely isolated and not conditioned. A total of 244 99mTc-radiopharmaceutical preparations (seven different types) have been tested and the radiochemical purity was checked at the end of preparation and until the expiry time. Moreover, we found that the mean temperature into the isolator was significantly higher than 25 °C, the temperature, in general, required for the preparation and storage of 99mTc-radiopharmaceuticals. Results confirmed the radiochemical stability of radiopharmaceutical products. However, as required in the field of quality assurance, the impact that different conditions than those required by the manufacturer on the radiopharmaceuticals quality have to be verified before human administration.

14 MeV Neutrons for 99Mo/99mTc Production: Experiments, Simulations and Perspectives.

BACKGROUND: the gamma-emitting radionuclide Technetium-99m (99mTc) is still the workhorse of Single Photon Emission Computed Tomography (SPECT) as it is used worldwide for the diagnosis of a variety of phatological conditions. 99mTc is obtained from 99Mo/99mTc generators as pertechnetate ion, which is the ubiquitous starting material for the preparation of 99mTc radiopharmaceuticals. 99Mo in such generators is currently produced in nuclear fission reactors as a by-product of 235U fission. Here we investigated an alternative route for the production of 99Mo by irradiating a natural metallic molybdenum powder using a 14-MeV accelerator-driven neutron source. METHODS: after irradiation, an efficient isolation and purification of the final 99mTc-pertechnetate was carried out by means of solvent extraction. Monte Carlo simulations allowed reliable predictions of 99Mo production rates for a newly designed 14-MeV neutron source (New Sorgentina Fusion Source). RESULTS: in traceable metrological conditions, a level of radionuclidic purity consistent with accepted pharmaceutical quality standards, was achieved. CONCLUSIONS: we showed that this source, featuring a nominal neutron emission rate of about 1015 s-1, may potentially supply an appreciable fraction of the current 99Mo global demand. This study highlights that a robust and viable solution, alternative to nuclear fission reactors, can be accomplished to secure the long-term supply of 99Mo.

Recent achievements in Tc-99m radiopharmaceutical direct production by medical cyclotrons.

99mTc is the most commonly used radionuclide in the field of diagnostic imaging, a noninvasive method intended to diagnose a disease, assess the disease state and monitor the effects of treatments. Annually, the use of 99mTc, covers about 85% of nuclear medicine applications. This isotope releases gamma rays at about the same wavelength as conventional X-ray diagnostic equipment, and owing to its short half-life (t½ = 6 h) is ideal for diagnostic nuclear imaging. A patient can be injected with a small amount of 99mTc and within 24 h almost 94% of the injected radionuclide would have decayed and left the body, limiting the patient's radiation exposure. 99mTc is usually supplied to hospitals through a 99Mo/99mTc radionuclide generator system where it is produced from the ß decay of the parent nuclide 99Mo (t½ = 66 h), which is produced in nuclear reactors via neutron fission. Recently, the interruption of the global supply chain of reactor-produced 99Mo, has forced the scientific community to investigate alternative production routes for 99mTc. One solution was to consider cyclotron-based methods as potential replacement of reactor-based technology and the nuclear reaction 100Mo(p,2n)99mTc emerged as the most worthwhile approach. This review reports some achievements about 99mTc produced by medical cyclotrons. In particular, the available technologies for target design, the most efficient extraction and separation procedure developed for the purification of 99mTc from the irradiated targets, the preparation of high purity 99mTc radiopharmaceuticals and the first clinical studies carried out with cyclotron produced 99mTc are described.

99mTc-labeled FAPI compounds for cancer and inflammation: from radiochemistry to the first clinical applications.

BACKGROUND: In recent years, fibroblast activating protein (FAP), a biomarker overexpressed by cancer-associated fibroblasts, has emerged as one of the most promising biomarkers in oncology. Similarly, FAP overexpression has been detected in various fibroblast-mediated inflammatory conditions such as liver cirrhosis and idiopathic pulmonary fibrosis. Along this trajectory, FAP-targeted positron emission tomography (PET), utilizing FAP inhibitors (FAPi) labeled with positron emitters, has gained traction as a powerful imaging approach in both cancer and inflammation. However, PET represents a high-cost technology, and its widespread adoption is still limited compared to the availability of gamma cameras. To address this issue, several efforts have been made to explore the potential of [99mTc]Tc-FAPi tracers as molecular probes for imaging with gamma cameras and single photon emission computed tomography (SPECT). MAIN BODY: Several approaches have been investigated for labeling FAPi-based compounds with 99mTc. Specifically, the mono-oxo, tricarbonyl, isonitrile, and HYNIC strategies have been applied to produce [99mTc]Tc-FAPi tracers, which have been tested in vitro and in animal models. Overall, these labeling approaches have demonstrated high efficiency and strong binding. The resulting [99mTc]Tc-FAPi tracers have shown high specificity for FAP-positive cells and xenografts in both in vitro and animal model studies, respectively. However, the majority of [99mTc]Tc-FAPi tracers have exhibited variable levels of lipophilicity, leading to preferential excretion through the hepatobiliary route and undesirable binding to lipoproteins. Consequently, efforts have been made to synthesize more hydrophilic FAPi-based compounds to improve pharmacokinetic properties and achieve a more favorable biodistribution, particularly in the abdominal region. SPECT imaging with [99mTc]Tc-FAPi has yielded promising results in patients with gastrointestinal tumors, demonstrating comparable or superior diagnostic performance compared to other imaging modalities. Similarly, encouraging outcomes have been observed in subjects with gliomas, lung cancer, breast cancer, and cervical cancer. Beyond oncological applications, [99mTc]Tc-FAPi-based imaging has been successfully employed in myocardial and idiopathic pulmonary fibrosis. CONCLUSIONS: This overview focuses on the various radiochemical strategies for obtaining [99mTc]Tc-FAPi tracers, highlighting the main challenges encountered and possible solutions when applying each distinct approach. Additionally, it covers the preclinical and initial clinical applications of [99mTc]Tc-FAPi in cancer and inflammation.

18 F-Choline Versus 68 Ga-PSMA-11 PET/CT Imaging Comparison in Incidental Clear Cell Renal Cell Carcinoma.

ABSTRACT: Few articles in literature describe the potential usefulness of 18 F-choline PET/CT and particularly 68 Ga-PSMA-11 PET/CT in imaging of clear cell renal cell carcinoma (ccRCC). We report a unique comparison in literature between the 2 radiotracers in a patient who underwent left nephrectomy with diagnosis of ccRCC, grade 3. 68 Ga-PSMA-11 PET/CT confirmed its emerging role in imaging ccRCC, as the incidentally detected renal neoplasm showed a significant higher uptake in comparison to 18 F-choline PET/CT, inducing surgical indication.

Misinterpretation of an inflammatory FDG uptake in a patient treated for Hodgkin lymphoma: a case report.

Hodgkin Lymphoma (HL) is a malignancy involving lymph nodes and lymphatic system. [18F]F-FDG PET/CT (FDG-PET) imaging is routinely used for staging, to assess early chemotherapy response (interim FDG-PET), at the end of treatment (EoT FDG-PET) and for the identification of disease recurrence. We present a case of a 39-year-old man treated for HL. FDG-PET scans performed after first line therapy (both Interim PET and at the end of therapy) demonstrated a persistent and significant mediastinal FDG uptake. The patient was treated with a second line therapy but the FDG-PET uptake did not change. After board discussion a new surgical, thoracoscopy-guided biopsy was performed. Histopathology demonstrated a dense fibrous tissue with occasional chronic inflammatory infiltrates. Persistent FDG-PET positivity may suggest refractory or relapsed disease. However, occasionally, non-malignant conditions are responsible for a persistent FDG uptake, not related to primary disease. An accurate evaluation of clinical history and previous imaging exams is mandatory for clinicians and others experts to avoid misinterpretations of FDG-PET results. Nevertheless, in some cases, only a more invasive procedure, such as a biopsy, may finally lead to a definitive diagnosis.

Oldie but Goodie: Is Technetium-99m Still a Treasure Trove of Innovation for Medicine? A Patents Analysis (2000-2022).

Technetium-99m is the workhorse of diagnostic nuclear medicine. The aim of the work is to analyze the technetium-99m patents since 2000 to photograph its innovation. QUESTEL's ORBIT Intelligence system was used for the collection of technetium inventions disclosed in patents and patent applications in more than 96 countries in the period 2000-2022; 2768 patent documents were analyzed. Patent counting and analysis have shown that SPECT imaging using technetium-99m radiopharmaceuticals is still robust. The introduction of new technetium-99m radiopharmaceuticals into clinical routine goes beyond successful trials. In eastern economies, such as China and other emerging markets, patent applications are on the rise, while those in developed western countries are stagnating, with some exceptions for the United States. But despite the difficulties, academic and industrial research on these tracers remains essential for the development of nuclear medicine.

Relevance of Volumetric Parameters Applied to [68Ga]Ga-DOTATOC PET/CT in NET Patients Treated with PRRT.

BACKGROUND: this study aims to explore the prognostic and predictive role of volumetric parameters on [68Ga]Ga-DOTATOC PET/CT in neuroendocrine tumors (NET) patients treated with peptide receptor radionuclide therapy (PRRT). METHODS: We retrospectively evaluated 39 NET patients (21 male, 18 female; mean age 60.7 y) within the FENET-2016 trial (CTiD:NCT04790708). PRRT was proposed with [177Lu]Lu-DOTATOC alone or combined with [90Y]Y-DOTATOC. [68Ga]Ga-DOTATOC PET/CT was performed at baseline and 3 months after PRRT. For each PET/CT, we calculated SUVmax, SUVmean, somatostatin receptor expressing tumor volume (SRETV), and total lesion somatostatin receptor expression (TLSRE), as well as their percentage of changes (Δ), both for liver (_L) and for total tumor burden (_WB). Early clinical response (3 months after PRRT) and PFS were evaluated according to RECIST 1.1 and institutional NET board. RESULTS: Early clinical response identified 9 partial response (PR), 25 stable disease (SD), and 5 progressive disease (PD). Post-SRETV_WB and ΔSRETV_WB were progressively increased among response groups (p = 0.02 and p = 0.03, respectively). Likewise, median post-SRETV_L was significantly higher in PD patients (p = 0.03). SUVmax and TLSRE did not correlate with early clinical response. Median PFS was 31 months. Patients with ΔSRETV_WB lower than -4.17% as well as those with post-SRETV_WB lower than 34.8 cm3 showed a longer PFS (p = 0.006 and p = 0.06, respectively). Finally, multivariate analysis identified ΔSRETV_WB as an independent predictor for PFS. CONCLUSIONS: our results could strengthen the importance of evaluating the burden of disease on [68Ga]Ga-DOTATOC PET/CT in NET patients treated with PRRT.