Studies to evaluate and optimize 177LuLu‐PSMA treatment focus primarily on individual patient data. A population pharmacokinetic (PK) dosimetry model was developed to explore the potential of using ...imaging data as input for population PK models and to characterize variability in organ and tumor uptake of 177LuLu‐PSMA‐617 in patients with low volume metastatic prostate cancer. Simulations were performed to identify the effect of dose adjustments on absorbed doses in salivary glands and tumors. A six‐compartment population PK model was developed, consisting of blood, salivary gland, kidneys, liver, tumor, and a lumped compartment representing other tissue (compartment 1–6, respectively), based on data from 10 patients who received 177LuLu‐PSMA‐617 (2 cycles, ~ 3 and ~ 6 GBq). Data consisted of radioactivity levels (decay corrected) in blood and tissues (9 blood samples and 5 single photon emission computed tomography/computed tomography scans). Observations in all compartments were adequately captured by individual model predictions. Uptake into salivary glands was saturable with an estimated maximum binding capacity (Bmax) of 40.4 MBq (relative standard error 12.3%) with interindividual variability (IIV) of 59.3% (percent coefficient of variation CV%). IIV on other PK parameters was relatively minor. Tumor volume was included as a structural effect on the tumor uptake rate constant (k15), where a two‐fold increase in tumor volume resulted in a 1.63‐fold increase in k15. In addition, interoccasion variability on k15 improved the model fit (43.5% CV%). Simulations showed a reduced absorbed dose per unit administered activity for salivary glands after increasing radioactivity dosing from 3 to 6 GBq (0.685 Gy/GBq vs. 0.421 Gy/GBq, respectively). All in all, population PK modeling could help to improve future radioligand therapy research.
Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a novel treatment for patients with castration-resistant prostate cancer (CRPC). Given the mode of action, patients in ...an earlier disease stage, such as hormone-sensitive prostate cancer (HSPC), are also likely to benefit from
LuLu-PSMA- (
Lu-PSMA) or
AcAc-PSMA-radioligand treatment (
Ac-PSMA). In this retrospective study, we analyzed the safety and efficacy of PSMA-RLT in early-stage and hormone-sensitive metastatic prostate cancer patients.
A retrospective study was performed in patients who received
Lu-PSMA and/or
Ac-PSMA with early-stage metastatic prostate cancer. The primary outcome parameter evaluated in this study was the progression-free survival (PFS) after PSMA-RLT and toxicity according to the Common Terminology Criteria for Adverse Events. Secondary outcome parameters were prostate-specific antigen (PSA) response and the date of onset of CRPC state.
In total, 20 patients were included of which 18 patients received
Lu-PSMA radioligand and two patients received tandem treatment with both
Lu-PSMA and
Ac-PSMA radioligands. Patients received a median of 2 treatment cycles (range 1-6) and a median activity of 6.2 GBq
Lu-PSMA per cycle (interquartile range (IQR) 5.2-7.4 GBq). PSMA-RLT was overall well-tolerated. The most common grade 1-2 side effects were xerostomia (
= 6) and fatigue (
= 8), which were only temporarily reported. One patient that received
Ac-PSMA developed grade 3-4 bone marrow toxicity. The median PFS was 12 months (95% confidence interval (CI), 4.09-19.9 months). Seventeen (85%) patients had a ≥50% PSA response following PSMA-RLT. One patient developed CRPC 9 months following PSMA-RLT.
In this small cohort study, PSMA-RLT appeared safe and showed encouraging efficacy for (metastasized) early-stage and hormone-sensitive prostate cancer patients. Prospective studies are awaited and should include long-term follow-up.
Bone scintigraphy is the standard procedure for the detection of bone metastases in breast cancer patients. FDG-PET/CT has been reported to be a sensitive tool for tumor staging in different ...malignant diseases. However, its accuracy for the detection of bone metastases has not been compared to bone scintigraphy.
To compare whole-body FDG-PET/CT and bone scintigraphy for the detection of bone metastases on a lesion basis in breast cancer patients.
Twenty-nine consecutive women (mean age 58 years, range 35-78 years) with histologically proven breast cancer were assessed with bone scintigraphy and whole-body FDG-PET/CT. Twenty-one patients (72%) were suffering from primary breast cancer and eight patients (28%) were in aftercare with a history of advanced breast cancer. Both imaging procedures were assessed for bone metastases by a radiologist and a nuclear medicine physician. Concordant readings between bone scintigraphy and FDG-PET/CT were taken as true. Discordant readings were verified with additional MRI imaging in all patients and follow-up studies in most patients.
A total of 132 lesions were detected on bone scintigraphy, FDG-PET/CT or both. According to the reference standard, 70/132 lesions (53%) were bone metastases, 59/132 lesions (45%) were benign, and three lesions (2%) remained unclear. The sensitivity of bone scintigraphy was 76% (53/70) compared to 96% (67/70) for FDG-PET/CT. The specificity of bone scintigraphy and FDG-PET/CT was 95% (56/59) and 92% (54/59), respectively. According to the reference standard bone metastases were present in eight out of the 29 patients (28%), whereas 20 patients (69%) were free of bone metastases. One (3%) patient had inconclusive readings on both modalities as well as on MRI and follow-up studies. Bone scintigraphy and FDG-PET/CT correctly identified seven out of eight patients with bone metastases and 20 out of 20 patients free of metastases.
On a lesion-basis whole-body FDG-PET/CT is more sensitive and equally specific for the detection of bone metastases compared with bone scintigraphy.
Background The aim of this study was to evaluate the value of 18F-FDG PET/CT (PET/CT) and MRI for local and/or whole-body restaging of adenoid cystic carcinoma of the head and neck (ACC). Methods ...Thirty-six patients with ACC underwent conventional MRI of the head and neck and a whole-body PET/CT and were analysed with regards to detection of a local tumor recurrence, lymph node or distant metastases. A consensus interpretation of all available imaging data was used as reference standard. Sensitivity, specificity, diagnostic accuracy, positive and negative predictive values were calculated for MRI and PET/CT. Results The sensitivity of PET/CT and MRI was 96% (89%), specificity 89% (89%), PPV 96% (96%), NPV 89% (73%) and accuracy 94% (89%) for detection of local tumors. Additionally, PET/CT revealed lymph node metastases in one patient and distant metastases in 9/36 patients. In three patients secondary primaries were found. Conclusions Whole-body PET/CT in addition to MRI of the head and neck improves detection of local tumour and metastastic spread in ACC. Keywords: PET/CT, MRI, Adenoid cystic carcinoma
Developing and optimizing targeted therapies in metastatic castration-resistant prostate cancer (mCRPC) necessitates molecular characterization. Obtaining sufficient tumor material for molecular ...characterization has been challenging. We aimed to identify clinical and imaging variables of imaging-guided bone biopsies in metastatic prostate cancer patients that associate with tumor yield and success in obtaining molecular results, and to design a predictive model: Clinical and imaging data were collected retrospectively from patients with prostate cancer who underwent a bone biopsy for histological and molecular characterization. Clinical characteristics, imaging modalities and imaging variables, were associated with successful biopsy results. In our study, we included a total of 110 bone biopsies. Histological conformation was possible in 84 of all biopsies, of which, in 73 of the 84, successful molecular characterization was performed. Prior use of PSMA PET-CT resulted in higher success rates in histological and molecular successful biopsies compared to CT or MRI. Evaluation of spine biopsies showed more often successful results compared to other locations for both histological and molecular biopsies (
= 0.027 and
= 0.012, respectively). Low Hounsfield units (HUs) and deviation (Dev), taken at CT-guidance, were associated with histological successful biopsies (
= 0.025 and
= 0.023, respectively) and with molecular successful biopsies (
= 0.010 and
= 0.006, respectively). A prediction tool combining low HUs and low Dev resulted in significantly more successful biopsies, histological and molecular (
= 0.023 and
= 0.007, respectively). Based on these results, we concluded that site selection for metastatic tissue biopsies with prior PSMA PET-CT imaging improves the chance of a successful biopsy. Further optimization can be achieved at CT-guidance, by selection of low HU and low Dev lesions. A prediction tool is provided to increase the success rate of bone biopsies in mCRPC patients, which can easily be implemented in daily practice.
Objective
To quantitatively analyze bone metastases from prostate cancer and correlate the apparent diffusion coefficients (ADCs) and standardized uptake values (SUVs).
Methods
Fifty-five patients ...with biopsy-proven prostate cancer or suspected recurrent prostate cancer were examined with simultaneous
18
F choline Positron emission tomography (PET)/MRI at 3 T. In 11 patients, thirty-two PET-positive bone lesions could be identified that were located in the field-of-view of the Diffusion weighted imaging-sequence. Region-of-interest and volume-of-interest analyses were performed to measure the mean and minimal ADCs and to assess maximum and mean SUVs of every bone lesion. Correlations between maximum and mean SUVs and mean and minimal ADCs were calculated.
Results
The SUV
max
of all lesions was 5.5 ± 3.1 (mean ± SD). The SUV
mean
was 1.8 ± 0.9. The mean ADC (ADC
mean
) of all lesions was 0.67 ± 0.13 × 10
−3
mm
2
/s. The minimal ADC (ADC
min
) of all lesions was 0.56 ± 0.14 × 10
−3
mm
2
/s. There was a moderate but significant inverse correlation of SUV
max
vs. ADC
mean
with a correlation coefficient of −0.4 (
p
= 0.02). There was also a significant inverse correlation of SUV
max
vs. ADC
min
with
r
= −0.41 (
p
= 0.02).
Conclusion
Our initial results demonstrate a moderate but significant inverse correlation between increased choline metabolism and ADC values of bone metastases from prostate cancer. Further research on a multimodality approach using simultaneous PET/MRI in bone metastasis of prostate cancer seems to be justified.
There is significant interest in a better understanding of the genetic underpinnings of the increased glucose metabolic rates of cancer cells. Thyroid cancer demonstrates a broad variability of ...(18)F-FDG uptake as well as several well-characterized oncogenic mutations. In this study, we evaluated the differences in glucose metabolism of the BRAF(V600E) mutation versus BRAF wild-type (BRAF-WT) in patients with metastatic differentiated thyroid cancer (DTC) and poorly differentiated thyroid cancer (PDTC).
Forty-eight DTC and 34 PDTC patients who underwent (18)F-FDG PET/CT for tumor staging were identified from a database search. All patients were tested for the BRAF(V600E) mutation and assigned to 1 of 2 groups: BRAF(V600E) mutated and BRAF-WT. (18)F-FDG uptake of tumor tissue was quantified by maximum standardized uptake value (SUVmax) of the hottest malignant lesion in 6 prespecified body regions (thyroid bed, lymph nodes, lung, bone, soft tissue, and other). When there were multiple lesions in 1 of the prespecified body regions, only the 1 with the highest (18)F-FDG uptake was analyzed.
In the DTC cohort, 24 tumors harbored a BRAF(V600E) mutation, whereas 24 tumors were BRAF-WT. (18)F-FDG uptake of BRAF(V600E)-positive lesions (median SUVmax, 6.3; n = 53) was significantly higher than that of BRAF-WT lesions (n = 39; median SUVmax, 4.7; P = 0.019). In the PDTC group, only 5 tumors were BRAF(V600E)-positive, and their (18)F-FDG uptake was not significantly different from the BRAF-WT tumors. There was also no significant difference between the SUVmax of all DTCs and PDTCs, regardless of BRAF mutational status (P = 0.90).
These data suggest that BRAF(V600E)-mutated DTCs are significantly more (18)F-FDG-avid than BRAF-WT tumors. The effect of BRAF(V600E) on tumor glucose metabolism in PDTC needs further study in larger groups of patients.
Objective
Pre-therapeutic blood dosimetry prior to a high-dose radioiodine therapy (RAIT) is recommended and a blood dose of 2 Gy is considered to be safe. In this study, changes in the blood cell ...count after radioiodine therapy of high risk differentiated thyroid carcinoma (DTC) were analyzed and compared with the results of the pre-therapeutic blood dosimetry using
124
I. Moreover, the influence of different modes of TSH stimulation and the number of preceding radioiodine therapies on the blood dose were assessed.
Methods
198 patients with locally advanced or metastasized DTC received a pre-therapeutic blood dosimetry using
124
I. To analyze the influence of the modes of TSH stimulation and the number of preceding RAITs on blood dose subgroups were built as follows: patients with endogenous TSH stimulation versus patients with exogenous TSH stimulation and patients with no preceding RAIT versus patients with at least one preceding RAIT. In 124/198 patients subsequent RAIT was performed. In 73/124 patients, hemograms were performed from day 2 to 12 month after RAIT.
Results
There was no high-grade bone marrow toxicity (i.e. ≥grade 3) in patients receiving less than 2 Gy blood dose—independent of the therapeutic history. Within the first month after radioiodine therapy, there was an overall decrease in the white blood cell and platelet counts. The erythrocyte count was essentially stable. There was a correlation between cell count decrease and predicted blood doses (Spearman’s correlation coefficient >−0.6 each) for the white cell line and the platelets. With regard to the subgroups, the blood dose per administered
131
I activity (BDpA) was significantly higher in patients with endogenous TSH stimulation (median 0.08 Gy/GBq) than in patients with exogenous TSH stimulation (0.06 Gy/GBq) and in patients with no previous RAIT (0.08 Gy/GBq) compared to patients who had previously undergone at least one RAIT (0.07 Gy/GBq).
Conclusions
The range of BDpA among DTC patients is rather wide. Our results suggest that lower blood doses can be expected when using exogenous TSH stimulation and blood doses are generally higher at first RAIT compared to subsequent RAITs. Thus, we advise to make blood dosimetry standard praxis prior to a high-activity RAIT.
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