Targeted radioligand therapy of metastatic castration-resistant prostate cancer (mCRPC) with 177Lu-PSMA (RLT) requires sufficient dose monitoring of the kidneys. Currently, dosimetry using SPECT/CT-imaging is the most preferred method. However, SPECT/CT is a time-consuming procedure and comprises additional radiation exposure to the patient. Moreover, not every therapeutic nuclear medicine facility has access to SPECT/CT. Therefore, the aim of this study was to develop a new procedure of kidney dosimetry without the use of SPECT/CT and evaluate this method in a large cohort of patients with mCRPC undergoing RLT. A dedicated torso phantom with kidneys filled with a solution of 177Lu-PSMA was used for quantitative calibration of a SPECT-camera. The calculated sensitivity was adapted according to the individual attenuation of the patient in four directions from the kidney surface to the body surface (ventral, dorsal, left and right) obtained from a previously performed CT. A total of 196 patients undergoing 926 cycles of 177Lu-PSMA therapy were retrospectively analyzed. Abdominal SPECT was performed 24, 48 and 72 h after administration of 177Lu-PSMA including scatter and dead-time correction in every patient. Kidney dose was calculated using an individual attenuation-based procedure and compared to values from international literature. Volumes of interest of the kidneys were drawn in the three sequential SPECT-images to calculate intra-renal effective half-life. Absolute quantification of activity in the kidneys was accomplished obtaining a patient individual sensitivity based on the individual attenuation in the patient. Kidney dose was then calculated applying a bi-exponential time activity curve in Microsoft EXCEL. Mean kidney dose per administered activity was 0.54 (± 0.26) Gy/GBq. With the presented procedure a reliable kidney dosimetry is possible without the use of SPECT/CT. Facilities without SPECT/CT are therefore able to perform an adequate kidney dosimetry without additional radiation exposure for the patient.
Ultrasound (US) has gained popularity as a guidance modality for percutaneous needle insertions because it is widely available and non-ionizing. However, coordinating scanning and needle insertion still requires significant experience. Current assistance solutions utilize optical or electromagnetic tracking (EMT) technology directly integrated into the US device or probe. This results in specialized devices or introduces additional hardware, limiting the ergonomics of both the scanning and insertion process. We developed the first ultrasound (US) navigation solution designed to be used as a non-permanent accessory for existing US devices while maintaining the ergonomics during the scanning process. A miniaturized EMT source is reversibly attached to the US probe, temporarily creating a combined modality that provides real-time anatomical imaging and instrument tracking at the same time. Studies performed with 11 clinical operators show that the proposed navigation solution can guide needle insertions with a targeting accuracy of about 5 mm, which is comparable to existing approaches and unaffected by repeated attachment and detachment of the miniaturized tracking solution. The assistance proved particularly helpful for non-expert users and needle insertions performed outside of the US plane. The small size and reversible attachability of the proposed navigation solution promises streamlined integration into the clinical workflow and widespread access to US navigated punctures.
This study aims to assess the change in uptake to reference organs, including the liver, parotid and salivary glands after radioligand therapy (RLT) with [177Lu]Lu-PSMA-617 in relation to pretreatment imaging metrics. Eighty-five patients with mCRPC underwent [68Ga]Ga-PSMA-11 PET/CT imaging prior to (pre RLT PET) and after (post RLT PET) a median of 3 (IQR 2-6) RLT cycles with [177Lu]Lu-PSMA-617. PSMA-positive tumor burden was stratified into 4 groups based on modified PROMISE criteria (oligofocal, multifocal, disseminated, diffuse). Uptake (SUVmean, SUVmax) in liver tissue, parotid and submandibular glands was measured. A control group was established with 54 patients who had received two separate PET acquisitions following the same protocol (PET1, PET2) within 12 months for localized or oligofocal prostate cancer without RLT in the interim. Baseline uptake values (SUVmean, SUVmax) in parotid (10.8 ± 3.2, 16.8 ± 5.4) and submandibular glands (11.3 ± 2.8, 18.1 ± 4.7) are 2-fold compared to liver uptake (4.9 ± 1.4, 7.7 ± 2.0), with no significant change between PET 1 and PET 2 in the control group. In the RLT group, increasing tumor burden class is significantly associated with decreasing uptake in the liver (p = 0.013), parotid (p < 0.001) and submandibular glands (p < 0.001); this tumor sink effect by respective tumor burden is widely maintained after RLT (p = 0.011, p < 0.001, p < 0.001). RLT has a significant impact on salivary gland uptake with decreasing values per patient in all groups of disease burden change (up to −30.4% in submandibular glands, p < 0.001), while liver tissue shows rising values in patients with declining tumor burden throughout RLT (+18.6%, p = 0.020). Uptake in liver tissue and salivary glands on [68Ga]Ga-PSMA-11 PET/CT imaging is inversely related to tumor burden prior to and following RLT with [177Lu]Lu-PSMA-617. Per patient, salivary gland uptake is further reduced throughout RLT independently from tumor burden, while changes in liver uptake remain burden-dependent. Liver and salivary gland uptake-derived metrics and segmentation thresholds may thus be of limited value when used as reference for response assessment to RLT.
Graves' disease is one of the most common causes of hyperthyroidism. Guideline recommendations advocate the intake of thionamides for at least 1 year. If hyperthyroidism persists, subsequent radioiodine-131 treatment (RIT) is a therapeutic option. Thionamides are known to influence intra-thyroidal bio-kinetics of iodine and should therefore be discontinued at least 3 days prior to RIT if possible. However, the required therapeutic activity has to be calculated individually by pre-therapeutic measurement of the uptake prior to RIT [radioiodine-131 uptake test (RIUT)] in Germany according to national guidelines. Therefore, the aim of this study was to quantify the influence of thionamides on intra-therapeutic uptake. A cohort of 829 patients with Graves' disease undergoing RIUT and RIT was analysed. Patients were subdivided into three groups. Group A: patients with carbimazole medication (n = 312), group B: patients with methimazole medication (n = 252) and group C: patients without thionamides (n = 265). Group A and B were further subdivided depending on the reduction of dosage of thionamides. In order to analyse the influence of thionamides, the variance of the determined individual extrapolated maximum intra-thyroidal uptake (EMU) between RIUT and RIT within the single groups and within the subgroups was statistically evaluated. When administering an equal dose of thionamides or no thionamides in RIUT and RIT (groups A1, B1 and C) no significant differences were detected when comparing EMU in RIT to EMU in RIUT (p > 0.05). In the subgroups A2-A4 (reduced dosage of carbimazole prior to RIT) EMU was significantly increased in RIT compared to RIUT [21% for a reduction of 0 to < 10 mg/d (A2), 39% for a reduction of 10-15 mg/d (A3) and 80% for a reduction of > 15 mg/d (A4)]. In the subgroups B2-B4 (reduced dosage of methimazole prior to RIT) EMU was as well significantly increased in RIT compared to RIUT [26% for a reduction of 0 to < 10 mg/d (B2), 36% for a reduction of 10-15 mg/d (B3) and 59% for a reduction of > 15 mg/d (B4)]. A significant dose-dependent increase of EMU in RIT compared to EMU in RIUT in patients discontinuing or reducing thionamides was detected. Therefore, thionamides should be discontinued at least 2 days prior to RIUT in order to achieve the designated target dose more precisely and to minimize radiation exposure of organs at risk.
177Lu-PSMA-617 radioligand therapy (177Lu-PSMA-RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC) currently consists of 4-6 cycles of 6.0-7.4 GBq of 177Lu-PSMA-617 each every 6-8 weeks. While safety and efficacy could be demonstrated in larger prospective trials irrespective of the tumor burden at 177Lu-PSMA RLT initiation, increased renal absorbed doses due to a reduced tumor sink effect in early responding, oligometastatic mCRPC patients pose difficulties. Response-adapted, dose distributing, intermittent treatment with up to six cycles has not been routinely performed, due to concerns about the potential loss of disease control. Treatment was discontinued in 19 early-responding patients with oligometastatic tumor burden after two (IQR 2-3) cycles of 177Lu-PSMA-RLT and 6.5 ± 0.7 GBq per cycle and resumed upon 68Ga-PSMA-11-PET/CT-based progression (according to the PCWG3 criteria). Subsequent treatment breaks were imposed if a PSMA-based imaging response could be achieved. A total of five (IQR 3-6) cycles reaching a cumulative activity of 32 ± 11 GBq were applied. A routine blood work-up including blood counts and liver and renal function was measured throughout the 177Lu-PSMA-RLT and follow-up to grade toxicity according to CTCAE v5.0 criteria. Survival outcome was calculated based on the Kaplan-Meier method. In total, treatment-free periods of 9 (IQR 6-17) cumulative months and the application of 177Lu-PSMA-RLT cycles over 16 (IQR 9-22) months could be achieved. Fifteen (84%) patients responded to subsequent cycles after the first treatment break and in 7/19 (37%) patients, intermittent 177Lu-PSMA-RLT consisted of ≥2 treatment breaks. The median PFS was 27 months (95% CI: 23-31) and overall survival was 45 months (95% CI: 28-62). No grade ≥3 hematological or renal toxicities could be observed during the 45 ± 21 months of follow-up. The cumulative mean renal absorbed dose was 16.7 ± 8.3 Gy and 0.53 ± 0.21 Gy/GBq. Intermittent radioligand therapy with 177Lu-PSMA-617 is feasible in early-responding patients with oligometastatic disease. A late onset of progression after subsequent cycles and the absence of significant toxicity warrants further investigation of the concept of intermittent treatment in selected patients.
Ziel/Aim Polidocanol provides an alternative to percutaneous ethanol instillation (PEI) in symptomatic cystic or predominantly cystic thyroid lesions. This study aims to investigate whether treatment efficacy of percutaneous polidocanol instillation (PPI) is maintained when applying a re-aspiration technique, whilst minimizing the risk of systemic side-effects.
Baseline uptake on prostate-specific membrane antigen (PSMA)-targeted imaging is a prerequisite for radioligand therapy (RLT) with [177Lu]Lu-PSMA-617. This study aims to quantify lesion-based response to RLT in relation to pretreatment standard molecular imaging metrics derived from [68Ga]Ga-PSMA-11 PET/CT. Sixty-one patients with mCRPC underwent [68Ga]Ga-PSMA-11 PET/CT imaging before and after a median of 4 (IQR 2−6) RLT cycles. Maximum and mean standardized uptake values (SUVmax, SUVmean), as well as tumor-to-liver ratio (TLR), were assessed. A median of 12 (IQR 7−17) lesions was analyzed per patient, resulting in a total of 718 lesions. Lesions with ≥30% SUVmax decline or falling below the blood pool uptake were considered responsive; ≥30% SUVmax increase marked lesion progression. Additionally, 4-point visual scoring was performed according to E-PSMA consensus. In total, 550/718 (76.6%) lesions responded to RLT, including 389/507 (76.7%) bone metastases and 143/181 (79.0%) lymph node metastases. Baseline SUVmax, SUVmean, and TLR values were associated with lesion response by a moderate but significant correlation (rs = 0.33, p < 0.001, rs = 0.32, p < 0.001, and rs = 0.31, p < 0.001, respectively). For the classification of lesion progression based on baseline PSMA uptake, receiver operating characteristics (ROC) found SUVmax, SUVmean, and TLR to have comparable discriminatory value (AUC 0.85, 0.87, and 0.83). Of 42 tumor sites with baseline uptake below the liver (V-score < 2), 19/42 (45.2%) were responsive, 9/42 (21.4%) were stable, and 14/42 (33.3%) showed progression, leaving liver uptake a threshold with low prognostic value for the identification of RLT-refractory lesions (PPV 33%). This was observed accordingly for various liver uptake-based thresholds, including TLR < 1.5, <2.0 with a PPV at 24%, 20%, respectively. Standard uptake parameters quantified by routine baseline [68Ga]Ga-PSMA-11 PET/CT are moderately associated with post-treatment lesion response to [177Lu]Lu-PSMA-617. Commonly applied liver-based uptake thresholds have limited value in predicting refractory lesions at individual tumor sites.
The study aimed to investigate heat sink effects in radiofrequency ablation (RFA) under thyroid-specific conditions. In an ex vivo model, bovine thyroid lobes were ablated using bipolar RFA with 2.0 kJ energy input at a power level set to 10 W (n = 35) and 25 W (n = 35). Glass vessels (3.0 mm outer diameter) placed within the ablation zone were used to deliver tissue perfusion at various flow rates (0, 0.25, 0.5, 1, 5, 10, 20 ml/min). Temperature was measured in the proximity of the vessel (T v ) and in the non-perfused contralateral region of the ablation zone (T c ), at equal distances to the ablation electrode (d = 8 mm). Maximum temperature within the perfused zone was significantly lowered with T v ranging from 54.1 ± 1.5 °C (20 ml/min) to 56.9 ± 1.5 °C (0.25 ml/min), compared to T c from 63.2 ± 3.5 °C (20 ml/min) to 63.2 ± 2.6 °C (0.25 ml/min) (10 W group). The cross-sectional ablation zone area decreased with increasing flow rates from 184 ± 12 mm 2 (0 ml/min) to 141 ± 20 mm 2 (20 ml/min) at 10 W, and from 207 ± 22 mm 2 (0 ml/min) to 158 ± 31 mm 2 (20 ml/min) in the 25 W group. Significant heat sink effects were observed under thyroid-specific conditions even at flow rates ≤ 1 ml/min. In thyroid nodules with prominent vasculature, heat dissipation through perfusion may therefore result in clinically relevant limitations to ablation efficacy.
Ziel/Aim Xerostomia is a known side-effect of 177Lu-PSMA radioligand therapy (177Lu-PSMA RLT) due to physiological PSMA expression in salivary glands. It remains unclear, whether the reported mouth dryness can be objectified by clinical function assessment. Therefore, the aim was to measure the function and PSMA expression of salivary glands and correlate the self-reported mouth dryness.
Ziel/Aim To evaluate the efficacy of radioiodine therapy (RIT) in patients with Graves´ disease (GD) and concomitant functioning nodules (Marine-Lenhart syndrome) with special focus on pre- and intratherapeutic dosimetry.
Key Clinical Message:In this case of struma ovarii a right-sided ovarian mass contained features of papillary thyroid cancer. Diagnostic iodine-123 revealed multiple foci of extraovarian spread, likely as a manifestation of concomitant peritoneal strumosis. Unilateral oophorectomy, partial peritonectomy, and adjuvant iodine-131 treatment were performed for successful curative treatment. Abstract:Struma ovarii is a rare form of mature teratoma defined by a predominance of thyroid tissue. Approximately 5% of all ovarian strumae exhibit malignant transformation. Due to their extreme rarity, there has been a lack of consensus concerning uniform diagnostic criteria. Appropriate, risk-stratified treatment strategies also remain widely unelaborated, based only on a small number of cases reported in the literature. We describe the case of a 35-year-old female, who presented after undergoing unilateral oophorectomy for a right-sided ovarian mass. Histological workup revealed a struma ovarii containing papillary thyroid cancer (PTC). Postoperative I-123 scintigraphy with single photon emission computed tomography (SPECT) detected multifocal extra-ovarian spread to the peritoneum, containing likely benign strumosis upon pathological examination. The subsequent treatment strategy involved an ablative concept including total thyroidectomy and subsequent I-131 radioiodine therapy. Throughout a 3-year follow-up, the patient has remained without recurrence with thyroglobulin levels ranging below detection limits. Surgical resection with adjuvant radioiodine therapy is a curative therapeutic strategy in cases of struma ovarii with thyroid-type carcinoma and peritoneal strumosis. Its benefits lay in avoiding more extensive surgery, potentially maintaining fertility, facilitating follow-up, and minimizing the risk of recurrence. Reliable criteria for risk stratification are needed to identify patients who are most likely to benefit from this treatment approach.
ZusammenfassungIn medizinisch begründeten Einzelfällen oder bei unbekannter Frühschwangerschaft kann es durch die Applikation offener radioaktiver Stoffe in der Nuklearmedizin zu einer pränatalen Strahlenexposition kommen. Die von Metabolisierung und Biodistribution abhängende Dosis für das Ungeborene kann messtechnisch nicht ermittelt werden. Eine möglichst valide Abschätzung der Dosis ist daher von großer Relevanz. Die Abschätzung erfolgt üblicherweise mit den biokinetischen und dosimetrischen Modellen der ICRP. Bei der Hybridbilddiagnostik muss zusätzlich auch die Strahlenexposition durch die radiologische Komponente berücksichtigt werden. Die Aktivität der im Rahmen einer nuklearmedizinischen Diagnostik applizierten offenen radioaktiven Stoffe führt üblicherweise zu einer Dosis des Ungeborenen von weniger als 20mSv. Relevante deterministische Strahlenwirkungen sind hier auszuschließen. Es ergeben sich keine praktischen Konsequenzen für den weiteren Verlauf der Schwangerschaft. Bei höheren Dosiswerten für das Ungeborene, wie sie insbesondere bei der therapeutischen Anwendung offener radioaktiven Stoffe bei unbekannter Schwangerschaft auftreten können, kann jedoch eine Dosis von 100mSv für das Ungeborene überschritten werden, welche als Schwelle für die Induktion von anatomischen Fehlbildungen, Wachstumshemmungen und funktionellen Störungen gilt.