Comparison of [99mTc]Tc-tilmanocept with [99mTc]Tc-sulphur colloids and [99mTc]Tc-albumin colloids for sentinel lymph node detection in patients with cutaneous malignancies of the head.

PURPOSE: Sentinel lymph node (SLN) biopsy is a staging procedure in the management of cutaneous malignancies of the head. The ideal radiopharmaceutical is controversial. This study aimed to compare [99mTc]Tc-tilmanocept (TcTM) with [99mTc]Tc-sulphur colloid (TcSC) and [99mTc]Tc-albumin colloid (TcAC) for SLN detection in the head and neck region. METHODS: Data from 62 patients with cutaneous malignancies of the head who were injected with TcTM, TcSC, or TcAC before SLN imaging (SLN-I) and SLN excision (SLN-E) between 2012 and 2021 were retrospectively analysed. SLN-I was performed using planar lymphoscintigraphy and SPECT/CT, and a gamma probe was used for SLN-E. The SLN-I localisation rate (patients with SLNs) and degree (SLN number) and SLN-E relocalisation rate (patients with SLNs) and ratio (SLN number in SLN-E/SLN number in SLN-I) were compared between TcTM, TcSC, and TcAC. RESULTS: TcTM showed similar SLN-I localisation rates for primaries in the anterior and posterior head region compared with TcSC (84.6% vs. 72.4%, p=0.680; both 100.0%) and TcAC (84.6% vs. 75.0%, p=1.000; both 100.0%). The SLN-I localisation degree for TcTM was higher for primaries in the anterior head region and similar for primaries in the posterior head region compared with TcSC (3.2 vs. 2.3, p=0.034; and 1.8 vs. 2.2, p=0.506) and TcAC (3.2 vs. 2.0, p=0.038; and 1.8 vs. 2.7, p=0.329). The SLN-E relocalisation rates and ratios were similar for all. CONCLUSION: On the basis of a limited study design that compared three different tracers in three different patient groups, TcTM showed comparable overall performance to TcSC and TcAC.

99mTc­labeled single-domain antibody for SPECT/CT assessment of HER2 expression in diverse cancer types.

The expression status of human epidermal growth factor receptor 2 (HER2) in cancer predicts response to HER2-targeted therapy. Therefore, its accurate determination is of utmost importance. In recent years, there has been an increase in research on noninvasive techniques for molecular imaging, as this method offers the advantages of a more accurate determination of HER2 status without the need for multiple biopsies. The technetium-labeled single-domain antibody RAD201, previously known as 99mTc-NM-02, has been shown to be safe for use in breast cancer imaging with reasonable radiation doses, favorable biodistribution, and imaging characteristics. METHODS: A total of six HER2-positive, heavily pretreated patients with different cancer types aged between 42 and 69 years (5 women and 1 man; the median age of 55.5) have been examined. In six of seven scans, the patients were administered 500 ml of Gelofusine® solution (40 mg/ml) for radiation protection before the tracer injection (434 ± 42 MBq). Planar scans were acquired with the patient supine at 10 min, 60 min, 160 min, 20 h, and 24 h after injection. A CT scan was acquired at 95 min, followed by local tomographic SPECT imaging. RESULTS: One patient was scanned twice with RAD201, 3 months apart, resulting in a total of seven scans for six patients. Here, we show that the use of RAD201 in our patient group shows the same favorable biodistribution as in a previous study with RAD201 (NCT04040686) and that the radiation dose to the critical organ kidney can be reduced by the application of the plasma expander Gelofusine® by almost 50%. CONCLUSION: RAD201 appears safe for use in humans and is a promising noninvasive tool for discriminating HER2 status in metastatic (breast) cancer, regardless of ongoing HER2-targeted antibody treatment.

68Ga-PSMA PET/CT for monitoring response to 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer.

PURPOSE: To evaluate the use of 68Ga-PSMA PET/CT for monitoring response to 177Lu-617 PSMA radioligand therapy in patients with metastatic castrate-resistant prostate cancer (mCRPC). METHODS: Patients from the University Hospital Bonn and the University Hospital Aachen were retrospectively reviewed for this study. We included 48 patients with mCRPC who were treated with 177Lu-PSMA-617 and whose records included 68Ga-PSMA PET/CT imaging before the first and after the third or fourth treatment cycle. A treatment response based on 68Ga-PSMA PET/CT was defined according to a modified version of the PERCIST criteria. A decline in PSA level of ≥50% was considered the reference standard. The sensitivity, specificity, positive and negative predictive values, and ROC curves were calculated, and patient survival times in relation to the PET results were also analysed. RESULTS: 68Ga-PSMA PET/CT had a sensitivity of about 85% and a specificity of between 55% and 65%. The negative and positive predictive values ranged between 70% and 78%. The fitted ROC area was 0.70. The survival time was about 19.6 months in patients with a treatment response, while nonresponders had a survival time of about 15.9 months. However, this difference between the groups was not statistically significant. CONCLUSION: Our results indicate that 68Ga-PSMA PET/CT could be a useful tool for the evaluation of response to 177Lu-PSMA-617 radioligand therapy within a theranostic framework.

Prostate-specific membrane antigen radioligand therapy of prostate cancer.

Defining an optimal therapeutic approach in metastatic castration-resistance prostate cancer (mCRPC) patients in advanced stages is still challenging in routine clinical practice. Prostate-specific membrane antigen (PSMA) targeted radionuclide therapy with ß- or α-emitters such as 177-Lutethium (177Lu) or 225-Actinium (225A) has been a main focus at multiple academic research centers in the last few years. This review article provides an overview of PSMA characteristics, clinical performance, safety and toxicity of PSMA targeted ß- or α-radiation therapy.

Multicentric 68Ga-PSMA PET radiomics for treatment response assessment of 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer.

Objective: The treatment with 177Lutetium PSMA (177Lu-PSMA) in patients with metastatic castration-resistant prostate cancer (mCRPC) has recently been approved by the FDA and EMA. Since treatment success is highly variable between patients, the prediction of treatment response and identification of short- and long-term survivors after treatment could help tailor mCRPC diagnosis and treatment accordingly. The aim of this study is to investigate the value of radiomic parameters extracted from pretreatment 68Ga-PSMA PET images for the prediction of treatment response. Methods: A total of 45 mCRPC patients treated with 177Lu-PSMA-617 from two university hospital centers were retrospectively reviewed for this study. Radiomic features were extracted from the volumetric segmentations of metastases in the bone. A random forest model was trained and validated to predict treatment response based on age and conventionally used PET parameters, radiomic features and combinations thereof. Further, overall survival was predicted by using the identified radiomic signature and compared to a Cox regression model based on age and PET parameters. Results: The machine learning model based on a combined radiomic signature of three features and patient age achieved an AUC of 0.82 in 5-fold cross-validation and outperformed models based on age and PET parameters or radiomic features (AUC, 0.75 and 0.76, respectively). A Cox regression model based on this radiomic signature showed the best performance to predict overall survival (C-index, 0.67). Conclusion: Our results demonstrate that a machine learning model to predict response to 177Lu-PSMA treatment based on a combination of radiomics and patient age outperforms a model based on age and PET parameters. Moreover, the identified radiomic signature based on pretreatment 68Ga-PSMA PET images might be able to identify patients with an improved outcome and serve as a supportive tool in clinical decision making.

Successful palliative peptide receptor radionuclide therapy for impending compression of vena cava due to unresectable liver metastasis of neuroendocrine tumor.

We present the case of a 77 year old male patient with metastatic pancreatic neuroendocrine tumor (NET). The patient was initially treated by extensive surgical resection that however, led to severe complications with delayed recovery. During follow-up, a number of new liver metastases were detected, one of which was in segment I with impending compression of the inferior vena cava. Due to age and general condition of the patient, instead of further surgical treatment, the patient received four cycles of 177Lu-DOTATOC resulting in an overall partial response with successful tumor reduction in liver segment I, resolving an impending compression of vena cava.

Dosing to rash?--The role of erlotinib metabolic ratio from patient serum in the search of predictive biomarkers for EGFR inhibitor-mediated skin rash.

AIM: The aim of this study was to investigate if biomarkers of individual drug metabolism, respectively, the erlotinib/O-desmethyl-erlotinib metabolic ratio, may be a predictive factor for the severity of erlotinib-mediated skin rash in epidermal growth factor receptor (EGFR) inhibitor-treated patients suffering from epithelial cancers. This is especially important since it is known that the severity of skin rash has a prognostic value on outcome and survival in cancer patients experiencing skin rash under treatment with EGFR inhibitors. METHODS: From 2008 to 2014, 96 patients, n = 63 suffering from histologically confirmed non-small-cell lung cancer and n = 33 from pancreatic adenocarcinoma were observed for the occurrence and severity of skin rash after the onset of treatment with erlotinib. The primary end-points (occurrence and severity of skin rash, progression-free survival [PFS] and overall survival [OS]) were analysed with regard to erlotinib and its metabolite O-desmethyl-erlotinib trough serum concentrations measured at 4 weeks after onset of therapy by the use of correlation, multiple regression and survival analysis. RESULTS: Occurrence of skin rash was associated with PFS (p = 0.0042) and OS (p = 0.017) in the overall cohort of erlotinib-treated cancer patients. Drug-metabolising activity assessed by the erlotinib/O-desmethyl-erlotinib metabolic ratio was correlated with severity of skin rash (p = 0.023) and as well highly associated with both PFS (p = 2.1 × 10(-4)) and OS (p = 5.8 × 10(-5)). CONCLUSION: The erlotinib/O-desmethyl-erlotinib metabolic ratio reflecting the individual metabolic activity of erlotinib correlated with the severity of skin rash and outcome in patients treated with EGFR tyrosine kinase inhibitors. The metabolic ratio determined in serum may be used for therapeutic monitoring in erlotinib treatment and decisions on individual dosing to rash in rash-negative patients.

Breast cancer imaging with PET and SPECT agents: an in vivo comparison.

UNLABELLED: Several radiopharmaceuticals and imaging techniques are proposed for breast cancer imaging. Since limited data are available of the uptake of SPECT and PET radiopharmaceuticals in malignant breast tumors and their metastases the aim of this study was to compare the uptake values and to correlate these data with imaging findings. METHODS: We have studied the uptake of F-18 FDG, Tc-99m MIBI and Tc-99m (V)DMSA in 31 tumors using immunosuppressed rats implanted with HH-16 clone 4 mammary tumor cells. Tumor gamma camera and PET imaging was performed to gain biokinetic data and uptake values by ROI-analysis. RESULTS: Tumor uptake was highest for F-18 FDG > Tc-99m (V)DMSA > Tc-99m MIBI. The uptake ratios (tumor to muscle) correlated well with the ratios calculated by ROI-analysis determined by imaging. CONCLUSIONS: In this in-vivo model, F-18 FDG revealed the best uptake and imaging properties and may be the radiopharmaceutical of choice for routine breast cancer imaging.

Palliation and survival after repeated (188)Re-HEDP therapy of hormone-refractory bone metastases of prostate cancer: a retrospective analysis.

UNLABELLED: This retrospective study compared the effects of single and multiple administrations of (186)Re-hydroxyethylidenediphosphonate ((186)Re-HEDP) on palliation and survival of prostate cancer patients presenting with more than 5 skeletal metastases. METHODS: A total of 60 patients were divided into 3 groups. Group A (n = 19) consisted of patients who had received a single injection; group B (n = 19), patients who had 2 injections; and group C (n = 22), patients who had 3 or more successive injections. The (188)Re-HEDP was prepared using non-carrier-added (188)Re obtained from an in-house (188)W/(188)Re generator after dilution with carrier perrhenate. Patients' data available from the referring physicians-including prostate-specific antigen levels-were entered into a Windows-based matrix and analyzed using a statistical program. The Gleason scores were similar for all 3 groups. RESULTS: Mean survival from the start of treatment was 4.50 ± 0.81 mo (95% confidence interval [CI], 2.92-6.08) for group A, 9.98 ± 2.21 mo (95% CI, 5.65-14.31) for group B, and 15.66 ± 3.23 (95% CI, 9.33-22.0) for group C. Although the 3 groups did not differ in Gleason score, the number of lost life-years was significantly lower in group C than in groups A and B. Pain palliation was achieved in 89.5% of group A, 94.7% of group B, and 90.9% of group C. CONCLUSION: Posttreatment overall survival could be improved from 4.50 to 15.66 mo by multiple-injection bone-targeted therapy with (188)Re-HEDP, when compared with a single injection. Significant pain palliation was common and independent of administration frequency.

Dose selection for radioiodine therapy of borderline hyperthyroid patients according to thyroid uptake of 99mTc-pertechnetate: applicability to unifocal thyroid autonomy?

PURPOSE: The aim of this study was to evaluate the feasibility of applying a previously described dose strategy based on (99m)Tc-pertechnetate thyroid uptake under thyrotropin suppression (TcTU(s)) to radioiodine therapy for unifocal thyroid autonomy. METHODS: A total of 425 consecutive patients (302 females, 123 males; age 63.1+/-10.3 years) with unifocal thyroid autonomy were treated at three different centres with (131)I, using Marinelli's formula for calculation of three different absorbed dose schedules: 100-300 Gy to the total thyroid volume according to the pre-treatment TcTU(s) (n=146), 300 Gy to the nodule volume (n=137) and 400 Gy to the nodule volume (n=142). RESULTS: Successful elimination of functional thyroid autonomy with either euthyroidism or hypothyroidism occurred at a mean of 12 months after radioiodine therapy in 94.5% of patients receiving 100-300 Gy to the thyroid volume, in 89.8% of patients receiving 300 Gy to the nodule volume and in 94.4% receiving 400 Gy to the nodule volume. Reduction in thyroid volume was highest for the 100-300 Gy per thyroid and 400 Gy per nodule strategies (36+/-19% and 38+/-20%, respectively) and significantly lower for the 300 Gy per nodule strategy (28+/-16%; p<0.01). CONCLUSION: A dose strategy based on the TcTU(s) can be used independently of the scintigraphic pattern of functional autonomous tissue in the thyroid.

Dose selection for radioiodine therapy of borderline hyperthyroid patients with multifocal and disseminated autonomy on the basis of 99mTc-pertechnetate thyroid uptake.

The aim of this study was to optimise radioiodine therapy of diffuse and nodular toxic goitre by calculation of the radiation dose delivered to the thyroid on the basis of the pretreatment technetium-99m pertechnetate thyroid uptake under thyrotropin suppression (TcTU(s)). The TcTU(s) value serves as a substitute for the non-suppressible iodine turnover and the functional autonomous mass. Marinelli's formula was used to calculate tissue absorbed doses of 150 Gy, 200 Gy, 250 Gy and 300 Gy to the thyroids of 438 patients with multifocal and disseminated autonomy. The mean age of patients was 70+/-9 years, and the mean thyroid volume was 54+/-26 ml. Two hundred and sixty-one of the patients had at least one documented previous episode of overt hyperthyroidism. Tissue absorbed doses were adapted to the pretreatment TcTU(s): 150 Gy for a TcTU(s) of 1.5%-2.49%, 200 Gy for a TcTU(s) of 2.5%-3.49%, 250 Gy for a TcTU(s) of 3.5%-4.49% and 300 Gy for a TcTU(s) of > or =4.5%. Normalisation of TcTU(s) and thyrotropin (TSH), thyroid volume reduction and frequency of hypothyroidism and recurrent hyperthyroidism were evaluated 1 year after a single radioiodine therapy. The presented dose strategy resulted in normalisation of TcTU(s) in 96% and an increase in TSH to the normal range in 92%. Recurrent hyperthyroidism was observed in only five patients. Thyroid volume decreased from 54+/-26 before treatment to 34+/-20 ml, a mean reduction of 37%. The frequency of hypothyroidism, at 0.9%, was encouragingly low. Dose selection in accordance with pretreatment TcTU(s) can be recommended for elimination of functional autonomous tissue with a single radioiodine therapy in patients of advanced age with enlarged thyroid glands and relevant autonomous masses who are at risk of developing iodine-induced hyperthyroidism.

Radioiodine therapy in Graves' disease based on tissue-absorbed dose calculations: effect of pre-treatment thyroid volume on clinical outcome.

This study was performed with three aims. The first was to analyse the effectiveness of radioiodine therapy in Graves' disease patients with and without goitres under conditions of mild iodine deficiency using several tissue-absorbed doses. The second aim was to detect further parameters which might be predictive for treatment outcome. Finally, we wished to determine the deviation of the therapeutically achieved dose from that intended. Activities of 185-2,220 MBq radioiodine were calculated by means of Marinelli's formula to deliver doses of 150, 200 or 300 Gy to the thyroids of 224 patients with Graves' disease and goitres up to 130 ml in volume. Control of hyperthyroidism, change in thyroid volume and thyrotropin-receptor antibodies were evaluated 15+/-9 months after treatment for each dose. The results were further evaluated with respect to pre-treatment parameters which might be predictive for therapy outcome. Thyroidal radioiodine uptake was measured every day during therapy to determine the therapeutically achieved target dose and its coefficient of variation. There was a significant dose dependency in therapeutic outcome: frequency of hypothyroidism increased from 27.4% after 150 Gy to 67.7% after 300 Gy, while the frequency of persistent hyperthyroidism decreased from 27.4% after 150 Gy to 8.1% after 300 Gy. Patients who became hypothyroid had a maximum thyroid volume of 42 ml and received a target dose of 256+/-80 Gy. The coefficient of variation for the achieved target dose ranged between 27.7% for 150 Gy and 17.8% for 300 Gy. When analysing further factors which might influence therapeutic outcome, only pre-treatment thyroid volume showed a significant relationship to the result of treatment. It is concluded that a target dose of 250 Gy is essential to achieve hypothyroidism within 1 year after radioiodine therapy in Graves' disease patients with goitres up to 40 ml in volume. Patients with larger goitres might need higher doses.