Next generation radiotheranostics promoting precision medicine.

Radiotheranostics is a field of rapid growth with some approved treatments including 131I for thyroid cancer, 223Ra for osseous metastases, 177Lu-DOTATATE for neuroendocrine tumors, and 177Lu-PSMA (prostate-specific membrane antigen) for prostate cancer, and several more under investigation. In this review, we will cover the fundamentals of radiotheranostics, the key clinical studies that have led to current success, future developments with new targets, radionuclides and platforms, challenges with logistics and reimbursement and, lastly, forthcoming considerations regarding dosimetry, identifying the right line of therapy, artificial intelligence and more.

EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds.

Primary liver tumours (i.e. hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC)) are among the most frequent cancers worldwide. However, only 10-20% of patients are amenable to curative treatment, such as resection or transplant. Liver metastases are most frequently caused by colorectal cancer, which accounts for the second most cancer-related deaths in Europe. In both primary and secondary tumours, radioembolization has been shown to be a safe and effective treatment option. The vast potential of personalized dosimetry has also been shown, resulting in markedly increased response rates and overall survival. In a rapidly evolving therapeutic landscape, the role of radioembolization will be subject to changes. Therefore, the decision for radioembolization should be taken by a multidisciplinary tumour board in accordance with the current clinical guidelines. The purpose of this procedure guideline is to assist the nuclear medicine physician in treating and managing patients undergoing radioembolization treatment. PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide among individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. These guidelines are intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set out in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognised that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

Correction to: Nuclear medicine services after COVID-19: gearing up back to normality.

The authors P. Orellana and N. El-Haj were inadvertently deleted in the original paper.

Longer-term recurrence rate after low versus high dose radioiodine ablation for differentiated thyroid Cancer in low and intermediate risk patients: a meta-analysis.

BACKGROUND: Regarding the longer-term recurrence rate the optimal activity for the remnant thyroid ablation in patients with differentiated thyroid cancer (DTC) is discussed controversially. For the short-term ablation success rate up to 12 months there are already several meta-analyses. In this study we performed the first meta-analysis regarding the longer-term recurrence rate after radioactive 131-I administration. METHODS: We conducted an electronic search using PubMed/MEDLINE, EMBASE and the Cochrane Library. All randomized controlled trials (RCTs) assessed the recurrence rate after radioactive iodine ablation in patients with DTC, with a follow-up of at least two years were selected. Statistics were performed by using Review Manager version 5.3 and Stata software. RESULTS: Four RCTs were included in the study, involving 1501 patients. There was no indication for heterogeneity (I2 = 0%) and publication bias. The recurrence rate among patients who had a low dose 131-iodine ablation was not higher than for a high dose activity (odds ratio (OR) 0.93 [95% confidence interval (CI) 0.53-1.63]; P = 0.79). The mean follow-up time was between 4.25 and 10 years. The subgroup analysis regarding the TSH stimulated thyroglobulin values (< 10 ng/mL versus < 2 ng/mL versus ≤1 ng/mL) showed no influence on recurrence rate. CONCLUSIONS: For the first time we showed that the longer-term, at least 2-year follow-up, recurrence rate among patients who had 131-iodine ablation with 1.1 GBq was not higher than with 3.7 GBq.

[Morphologic diagnostic criteria of noninvasive follicular neoplasia with papillary-like nuclear features (NIFTP) : A diagnostic challenge for the patient's benefit]. / Morphologische Diagnosekriterien der nichtinvasiven follikulären Neoplasie mit PTC-äquivalenten Kernmerkmalen (NIFTP) : Eine diagnostische Herausforderung zum Nutzen des Patienten.

The major goals of the introduction of the noninvasive follicular neoplasia with papillary-like nuclear features (NIFTP) are to spare patients with a biologically indolent subgroup of the follicular variant of papillary carcinoma (FV-PTC) both overtreatment and the psychologically burden of a cancer/carcinoma diagnosis. However, strict histological and molecular pathological criteria have been introduced for the diagnosis of NIFTP. NIFTP tumors may be a few millimeters in diameter, but may also measure more than 4 cm. Histologically, an encapsulated/clearly demarcated lesion with (>70%) follicular structure and the nuclear characteristics of PTC must be present as a prerequisite; invasion of capsule/vessels must be excluded as well as significant proportions (>30%) showing a solid/trabecular/insular growth pattern, psammoma bodies, tumor necrosis, an increased mitotic rate (>3/10 HPF), and/or a BRAF V600E mutation. The establishment of the NIFTP necessitated a redefinition of the diagnostic criteria of PTC and has implications on the evaluation of fine needle biopsy (FNB) of the thyroid gland. Although a prediction is difficult, the correct diagnosis of NIFTP could lead to a 10-20% reduction in thyroid carcinoma incidence.

11C-MET PET/MRI for detection of recurrent glioma.

INTRODUCTION: Radiological assessment of brain tumors is widely based on the Radiology Assessment of Neuro-Oncology (RANO) criteria that consider non-specific T1 and T2 weighted images. Limitation of the RANO criteria is that they do not include metabolic imaging techniques that have been reported to be helpful to differentiate treatment related changes from true tumor progression. In the current study, we assessed if the combined use of MRI and PET with hybrid 11C-MET PET/MRI can improve diagnostic accuracy and diagnostic confidence of the readers to differentiate treatment related changes from true progression in recurrent glioma. METHODS: Fifty consecutive patients with histopathologically proven glioma were prospectively enrolled for a hybrid 11C-MET PET/MRI to differentiate recurrent glioma from treatment induced changes. Sole MRI data were analyzed based on RANO. Sole PET data and in a third evaluation hybrid 11C-MET-PET/MRI data were assessed for metabolic respectively metabolic and morphologic glioma recurrence. Diagnostic performance and diagnostic confidence of the reader were calculated for the different modalities, and the McNemar test and Mann-Whitney U Test were applied for statistical analysis. RESULTS: Hybrid 11C-MET PET/MRI was successfully performed in all 50 patients. Glioma recurrence was diagnosed in 35 of the 50 patients (70%). Sensitivity and specificity were calculated for MRI (86.11% and 71.43%), for 11C-MET PET (96.77% and 73.68%), and for hybrid 11C-MET-PET/MRI (97.14% and 93.33%). For diagnostic accuracy hybrid 11C-MET-PET/MRI (96%) showed significantly higher values than MRI alone (82%), whereas no significant difference was found for 11C-MET PET (88%). Furthermore, by rating on a five-point Likert scale significantly higher scores were found for diagnostic confidence when comparing 11C-MET PET/MRI (4.26 ± 0,777) to either PET alone (3.44 ± 0.705) or MRI alone (3.56 ± 0.733). CONCLUSION: This feasibility study showed that hybrid PET/MRI might strengthen RANO classification by adding metabolic information to conventional MRI information. Future studies should evaluate the clinical utility of the combined use of 11C-MET PET/MRI in larger patient cohorts.

Cardiac 4D phase-contrast CMR at 9.4 T using self-gated ultra-short echo time (UTE) imaging.

BACKGROUND: Time resolved 4D phase contrast (PC) cardiovascular magnetic resonance (CMR) in mice is challenging due to long scan times, small animal ECG-gating and the rapid blood flow and cardiac motion of small rodents. To overcome several of these technical challenges we implemented a retrospectively self-gated 4D PC radial ultra-short echo-time (UTE) acquisition scheme and assessed its performance in healthy mice by comparing the results with those obtained with an ECG-triggered 4D PC fast low angle shot (FLASH) sequence. METHODS: Cardiac 4D PC CMR images were acquired at 9.4 T in healthy mice using the proposed self-gated radial center-out UTE acquisition scheme (TE/TR of 0.5 ms/3.1 ms) and a standard Cartesian 4D PC imaging sequence (TE/TR of 2.1 ms/5.0 ms) with a four-point Hadamard flow encoding scheme. To validate the proposed UTE flow imaging technique, experiments on a flow phantom with variable pump rates were performed. RESULTS: The anatomical images and flow velocity maps of the proposed 4D PC UTE technique showed reduced artifacts and an improved SNR (left ventricular cavity (LV): 8.9 ± 2.5, myocardium (MC): 15.7 ± 1.9) compared to those obtained using a typical Cartesian FLASH sequence (LV: 5.6 ± 1.2, MC: 10.1 ± 1.4) that was used as a reference. With both sequences comparable flow velocities were obtained in the flow phantom as well as in the ascending aorta (UTE: 132.8 ± 18.3 cm/s, FLASH: 134.7 ± 13.4 cm/s) and pulmonary artery (UTE: 78.5 ± 15.4 cm/s, FLASH: 86.6 ± 6.2 cm/s) of the animals. Self-gated navigator signals derived from information of the oversampled k-space center were successfully extracted for all animals with a higher gating efficiency of time spent on acquiring gated data versus total measurement time (UTE: 61.8 ± 11.5%, FLASH: 48.5 ± 4.9%). CONCLUSIONS: The proposed self-gated 4D PC UTE sequence enables robust and accurate flow velocity mapping of the mouse heart in vivo at high magnetic fields. At the same time SNR, gating efficiency, flow artifacts and image quality all improved compared to the images obtained using the well-established, ECG-triggered, 4D PC FLASH sequence.

Recommended administered activities for (68)Ga-labelled peptides in paediatric nuclear medicine.

PURPOSE: The aim of this study was to establish a method for determining administered activities for (68)Ga-labelled peptides. Dose calculations were based on the weight-independent effective dose model proposed by the EANM paediatric dosage card for use in paediatric nuclear medicine. METHODS: Previously published time-integrated activity coefficients for (68)Ga-DOTATATE, (68)Ga-DOTATOC and (68)Ga-pentixafor were used to calculate age-independent effective doses. Consequently, the corresponding weight-dependent effective dose coefficients were rescaled according to the formalism of the EANM dosage card to determine the radiopharmaceutical class of  (68)Ga-labelled peptides ("multiples") and to calculate the baseline activities based on an upper limit for administered activity (185 MBq) in an adult. RESULTS: All calculated normalization factors suggest that the (68)Ga-labelled peptides are class "B" radiopharmaceuticals. The baseline activity for all compounds is 12.8 MBq. In analogy to (18)F-fluoride, we recommend a minimum activity of 14 MBq. CONCLUSION: For paediatric nuclear medicine applications involving (68)Ga-labelled peptides, we suggest determining administered activities based on the formalism proposed in this work. The corresponding effective doses from these procedures will remain age-independent.

Multi-technique hybrid imaging in PET/CT and PET/MR: what does the future hold?

Integrated positron-emission tomography and computed tomography (PET/CT) is one of the most important imaging techniques to have emerged in oncological practice in the last decade. Hybrid imaging, in general, remains a rapidly growing field, not only in developing countries, but also in western industrialised healthcare systems. A great deal of technological development and research is focused on improving hybrid imaging technology further and introducing new techniques, e.g., integrated PET and magnetic resonance imaging (PET/MRI). Additionally, there are several new PET tracers on the horizon, which have the potential to broaden clinical applications in hybrid imaging for diagnosis as well as therapy. This article aims to highlight some of the major technical and clinical advances that are currently taking place in PET/CT and PET/MRI that will potentially maintain the position of hybrid techniques at the forefront of medical imaging technologies.

Fixed ratio dosing of pramlintide with regular insulin before a standard meal in patients with type 1 diabetes.

Amylin is co-secreted with insulin and is therefore lacking in patients with type 1 diabetes. Replacement with fixed ratio co-administration of insulin and the amylin analogue pramlintide may be superior to separate dosing. This concept was evaluated in a ratio-finding study. Patients with type 1 diabetes were enrolled in a randomized, single-masked, standard breakfast crossover study using regular human insulin injected simultaneously with pramlintide 6, 9 or 12 mcg/unit insulin or placebo. Insulin dosage was reduced by 30% from patients' usual estimates. Plasma glucose, glucagon and pramlintide and adverse events were assessed. All ratios reduced 0-3-h glucose and glucagon increments by >50%. No hypoglycaemia occurred. Adverse events were infrequent and generally mild. All pramlintide/insulin ratios markedly and safely reduced glycaemic excursions and suppressed glucagon secretion in the immediate postprandial state. Further study using one of these ratios to explore the efficacy and safety of longer-term meal-time and basal hormone replacement is warranted.

[Flexor tendon transplantation]. / Beugesehnentransplantation.

BACKGROUND: Insufficiency of both flexor tendons of a finger considerably disrupts the function of the whole hand. Flexor tendon transplantation represents the best way to reconstruct or improv function in many cases. OBJECTIVES: Based on the literature and our own results, not only the current state of the surgical technique, but also the opportunities and dangers of this sophisticated operation, are represented. Knowledge of alternative methods is important. METHODS: With a follow-up of between 2 to 12 years, a total of 272 patients who underwent flexor tendon transplantation in the hand during several periods from 1974 to 2000 were investigated. RESULTS: Similar to the international literature, our long-term results did not specify the exact surgical technique (pedicled or free). According to the Buck-Gramcko score, 32 % had very good results, 26.4 % good, 15.1 % satisfactory, and 26.5 % poor. CONCLUSIONS: Numerous details need to be considered before, during, and after surgery. For the patient, the procedure has tremendous significance in many ways; thus, this operation should only be performed by an experienced hand surgeon.

[Suture techniques for flexor tendons of the hand]. / Nahttechniken für Beugesehnen der Hand.

BACKGROUND: The success of the flexor tendon suture depends on many factors. An important factor is that the tendon suture technique that must be carried out for flexor tendons is considerably more complex and more precise than for all other tendons of the body. OBJECTIVES: To discover important technical points that need to be considered during flexor tendon suturing. METHOD: We compiled the most important technical details in flexor tendon suturing from the literature and from personal experience. RESULTS: Details on core suture, peripheral suture, the tensile strength, gapping, the circulation of sutured tendons, gliding resistance and excisions are discussed. CONCLUSIONS: Flexor tendon suturing must be performed taking great care to conserve tissue.

[Pulley reconstruction in the hand]. / Ringbandrekonstruktion an der Hand.

BACKGROUND: To ensure proper function of the flexor tendons, pulleys are extremely important. Pulleys can be impaired by injury, infection, but also sometimes iatrogenically. The consequences of this failure are often poorly understood. OBJECTIVES: What is the impact of pulley insufficiency, what are the clinical signs, and what are the reconstruction options? METHODS: The experiences of 64 patients with different forms of pulley insufficiency are presented. RESULTS: All patients benefit from a ring ligament reconstruction. A phalanx fracture can be one complication. CONCLUSIONS: Pulley reconstructions are very beneficial operations.

[Water-cooled laser sealing of lung tissue in an ex-vivo ventilated porcine lung model]. / Wassergekühlte Laserversiegelung von Lungengewebe am ex vivo ventilierten Schweinelungenmodell.

INTRODUCTION: Laser resections of lung metastases are followed by air leaks from the parenchymal defect. Large surfaces after metastasectomy are closed by sutures or sealants while smaller areas are frequently sealed thermally by cautery or laser. In this study two different techniques of thermal sealing of lung tissue with laser light are investigated. AIM AND METHODS: Carbonisation of lung tissue during thermal sealing appears at temperatures higher than 180 °C. Hypothetically this is contraproductive to haemo- as well as to pneumostasis. In this experimental study thermal laser sealing with and without carbonisation is investigated. In one series tissue temperatures higher than 100 °C are avoided by water dropping from the tip of the light guide onto the parenchymal leak. In the other series carbonisation appeared because the laser light was applied in the non-contact mode without tissue cooling. The characteristics of the laser were 40 W, 1350 nm continuous mode. Air leaks (Vt) were measured with a simple and fast technique with high precision. The sealing effect of either series was defined as S = (1-Vt/V0) and the difference of S was statistically examined. RESULTS: The basic values V0 before sealing were about the same in both series. The air leaks Vt after 15, 30 and 45 s of sealing varied significantly in both series (p = 0.03). During simultaneous cooling the sealing effect was increasing with the duration of laser application, while it became worse in the series without cooling. Histological examination of the sealing zone showed only coagulation of the tissue, while ruptured alveolae could be seen more often in the non-cooled sealing area. DISCUSSION: It could be shown in the ex-vivo lung model that laser sealing of parenchymal leaks is improved by simultaneous cooling during laser application. Non cooled laser sealing seems to heat up the tissue abruptly and create carbonisation followed by multiple ruptures of alveola and small airways. In accordance with our clinical experience this experimental study confirms that laser sealing for pneumostasis after metastasectomy can be improved by simultaneously cooling the resection area when treated with the laser.