Peptide-receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs such as octreotide is an effective therapy against neuroendocrine tumors. Other radiolabeled peptides and antibody ...fragments are under investigation. Most of these compounds are cleared through the kidneys and reabsorbed and partially retained in the proximal tubules, causing dose-limiting nephrotoxicity. An overview of renal handling of radiolabeled peptides and resulting nephrotoxicity is presented, and strategies to reduce nephrotoxicity are discussed. Modification of size, charge, or structure of radiolabeled peptides can alter glomerular filtration and tubular reabsorption. Coinfusion of competitive inhibitors of reabsorption also interferes with the interaction of peptides with renal endocytic receptors; coinfusion of basic amino acids is currently used for kidney protection in clinical PRRT. Furthermore, nephrotoxicity may be reduced by dose fractionation, use of radioprotectors, or use of mitigating agents. Decreasing the risk of nephrotoxicity allows for administration of higher radiation doses, increasing the effectiveness of PRRT.
To evaluate the impact of Gallium-68
Ga labeled prostate specific membrane antigen (PSMA) positron emission tomography (PET)/X-ray computed tomography (CT) compared with conventional imaging on ...staging and clinical management of men evaluated for primary prostate cancer (PCa).
Men with newly diagnosed biopsy-proven PCa who had been staged with a conventional staging protocol including bone scintigraphy (BS) and additionally underwent
GaPSMA PET/CT, were evaluated retrospectively. Imaging findings from BS, magnetic resonance imaging (MRI) and/or CT were categorized regarding locoregional nodal (N) and distant metastasis (M) status as negative, positive or equivocal before and after addition of the information of PET/CT. Also, the imaging-based level of confidence (LoC) in correct assessment of N and M status was scored. Impact of PET/CT on clinical management was evaluated by the percentage of treatment category changes after PET/CT as determined in the multidisciplinary tumour board.
Sixty-four men with intermediate and high-risk PCa were evaluated. With additional information of PET/CT, N status was upstaged in 23%, and downstaged in 9%. M status was upstaged in 13%, and downstaged in 23%. A net increase in LoC of 20% was noted, mainly regarding M status. Treatment category changed from palliative to curative in 9%, and from curative to palliative in 3%. An undecided treatment plan changed to curative in 14%, as well as to palliative in another 9%. In total, a 36% treatment category change was noted. High negative predictive value of PET/CT for M status was indicated by 27 patients that underwent robot-assisted radical prostatectomy and reached postoperative biochemical disease-free status or had a likely other site of disease recurrence.
PSMA PET/CT can cause considerable changes in N and M staging, as well as in management compared to conventional staging. Findings of this study support the replacement of BS and CT by PSMA PET/CT in staging primary PCa.
Background
The role of
18
F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) and staging laparoscopy (SL) has increased in the preoperative staging of gastric ...cancer. Dutch national guidelines have recommended the use of FDG-PET/CT and SL for patients with locally advanced tumors since July 2016.
Objective
The aim of this study was to evaluate the implementation of FDG-PET/CT and SL in The Netherlands.
Methods
Between 2011 and 2018, all patients who underwent surgery for gastric cancer were included from the Dutch Upper GI Cancer Audit. The use of FDG-PET/CT and SL was evaluated before and after revision of the Dutch guidelines. Outcomes included the number of non-curative procedures (e.g. palliative and futile procedures) and the association of FDG-PET/CT and SL, with waiting times from diagnosis to the start of treatment.
Results
A total of 3310 patients were analyzed. After July 2016, the use of FDG-PET/CT (23% vs. 61%;
p
< 0.001) and SL (21% vs. 58%;
p
< 0.001) increased. FDG-PET/CT was associated with additional waiting time to neoadjuvant therapy (4 days), as well as primary surgical treatment (20 days), and SL was associated with 8 additional days of waiting time to neoadjuvant therapy. Performing SL or both modalities consecutively in patients in whom it was indicated was not associated with the number of non-curative procedures.
Conclusion
During implementation of FDG-PET/CT and SL after revision of the guidelines, both have increasingly been used in The Netherlands. The addition of these staging methods was associated with increased waiting time to treatment. The number of non-curative procedures did not differ after performing none, solely one, or both staging modalities.
Prostate-specific membrane antigen (PSMA) targeted tracers show increased uptake in several malignancies, indicating a potential for peptide radioligand therapy. Intra-arterial injection of ...radiotracers can increase the therapeutic window. This study aimed to evaluate the feasibility of intra-arterial injection of
68
GaGa-PSMA-11 for intrahepatic cholangiocarcinoma and compare tracer uptake after intrahepatic arterial injection and intravenous injection. Three patients with intrahepatic cholangiocarcinoma received
68
GaGa-PSMA-11 through a hepatic arterial infusion pump, followed by positron emission tomography/computed tomography (PET/CT). Two-three days later, patients underwent PET/CT after intravenous
68
GaGa-PSMA-11 injection. All tumours showed higher uptake on the intra-arterial scan compared with the intravenous scan: the intra-arterial / intravenous standardised uptake value normalised by lean body mass ratios were 1.40, 1.46, and 1.54. Local intra-arterial PSMA injection is possible in patients with intrahepatic cholangiocarcinoma. Local injection increases tumour-to-normal tissue ratios, increasing the therapeutic window for theranostic applications.
Relevance statement
Intra-arterial Prostate specific membrane antigen (PSMA) injection increases the therapeutic window for potential theranostic application in intrahepatic cholangiocarcinoma.
Key Points
Three patients with intrahepatic cholangiocarcinoma underwent PET/CT after intra-arterial and intravenous injection of
68
GaGa-PSMA-11.
Intra-arterial injection showed higher uptake than intravenous injection.
PSMA-targeted imaging could be valuable for a subset of intrahepatic cholangiocarcinoma patients.
Graphical Abstract
Purpose
In about 30% of patients treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection for locally advanced oesophageal cancer no vital tumour is found in the resection ...specimen. Accurate clinical response assessment is critical if deferral from surgery is considered in complete responders. Our study aimed to compare the performance of MRI and of FDG-PET/CT for the detection of residual disease after nCRT.
Methods
Patients with oesophageal cancer eligible for nCRT and oesophagectomy were prospectively included. All patients underwent FDG-PET/CT and MRI before and between 6 and 8 weeks after nCRT. Two radiologists scored the MRI scans, and two nuclear medicine physicians scored the FDG-PET/CT scans using a 5-point score for residual disease. Histopathology after oesophagectomy represented the reference standard. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated for detection of residual tumour (ypT+), residual nodal disease (ypN+), and any residual disease (ypT+Nx/ypT0N+).
Results
Seven out of 33 (21%) patients had a pathological complete response. The AUCs for individual readers to detect ypT+ were 0.71/0.70 on diffusion-weighted (DW)-MRI and 0.54/0.57 on FDG-PET/CT, and to detect ypN+ were 0.89/0.81 on DW-MRI and 0.75/0.71 on FDG-PET/CT. The AUCs/sensitivities/specificities for the individual readers to detect any residual disease were 0.74/92%/57% and 0.70/96%/43% on MRI; these were 0.49/69%/29% and 0.60/69%/43% on FDG-PET/CT, respectively.
Conclusion
MRI reached higher diagnostic accuracies than FDG-PET/CT for the detection of residual tumour in oesophageal cancer patients at 6 to 8 weeks after nCRT.
Objective
Abdominal cancer patients increasingly undergo multimodality imaging. This study evaluates effects of integrated reading of PET/CT and abdominal MRI on staging outcomes and diagnostic ...confidence compared to “routine” separate reading.
Methods
In total,
N
= 201 patients who underwent abdominal MRI and whole-body F-18 FDG-PET/CT within 14 days were retrospectively analyzed. Original MRI and PET/CT reports were retrieved and reported findings translated into a 5-point confidence score (1 = definitely benign to 5 = definitely malignant) for 7 standardized regions (primary tumor/regional lymph nodes/distant lymph nodes/liver/lung/bone/peritoneum) per patient. Two-reader teams (radiologist + nuclear medicine physician) then performed integrated reading of the images using the same scoring system.
Results
Integrated reading led to discrepant findings in 59 of 201 (29%) of patients, with potential clinical impact in 25 of 201 (12%). Equivocal scores decreased from 5.7% (PET/CT) and 5.4% (MRI) to 3.2% (
p
= 0.05 and
p
= 0.14). Compared to the original PET/CT reports, integrated reading led to increased diagnostic confidence in 8.9% versus decreased confidence in 6.6% (
p
= 0.26). Compared with the original MRI reports, an increase in confidence occurred in 9.6% versus a decrease in 6.9% (
p
= 0.18). The effect on diagnostic confidence was most pronounced in lymph nodes (
p
= 0.08 vs. MRI), cervical cancer (
p
= 0.03 vs. MRI), and recurrent disease staging (
p
= 0.06 vs. PET/CT).
Conclusions
Integrated PET/CT+MRI reading alters staging outcomes in a substantial proportion of cases with potential clinical impact in ± 1 out of 9 patients. It can also have a small positive effect on diagnostic confidence, particularly in lymph nodes and cervical cancer, and in post-treatment settings. These findings support further collaboration between radiology and nuclear medicine disciplines.
Key Points
• Increasing numbers of patients undergo multimodality imaging consisting of both MRI and PET/CT for staging of abdominal malignancies.
• Integrated reading of FDG-PET/CT and abdominal MR images by a team, consisting of a radiologist and a nuclear medicine physician, can alter staging outcomes compared to separate reporting of the exams in a substantial proportion of cases and with potential clinical impact in ± 1 out of 9 patients.
• Integrated PET/CT+MRI reading can have a small positive effect on diagnostic confidence.
Background
New digital detectors and block-sequential regularized expectation maximization (BSREM) reconstruction algorithm improve positron emission tomography (PET)/magnetic resonance (MR) image ...quality. The impact on image quality may differ from analogue PET/computed tomography (CT) protocol. The aim of this study is to determine the potential reduction of injected
68
GaGa-DOTA-TATE activity for digital PET/MR with BSREM reconstruction while maintaining at least equal image quality compared to the current analogue PET/CT protocol.
Methods
NEMA IQ phantom data and 25 patients scheduled for a diagnostic PET/MR were included. According to our current protocol, 1.5 MBq
68
GaGa-DOTA-TATE per kilogram (kg) was injected. After 60 min, scans were acquired with 3 (≤ 70 kg) or 4 (> 70 kg) minutes per bedposition. PET/MR scans were reconstructed using BSREM and factors
β
150, 300, 450 and 600. List mode data with reduced counts were reconstructed to simulate scans with 17%, 33%, 50% and 67% activity reduction. Image quality was measured quantitatively for PET/CT and PET/MR phantom and patient data. Experienced nuclear medicine physicians performed visual image quality scoring and lesion counting in the PET/MR patient data.
Results
Phantom analysis resulted in a possible injected activity reduction of 50% with factor
β
= 600. Quantitative analysis of patient images revealed a possible injected activity reduction of 67% with factor
β
= 600. Both with equal or improved image quality as compared to PET/CT. However, based on visual scoring a maximum activity reduction of 33% with factor
β
= 450 was acceptable, which was further limited by lesion detectability analysis to an injected activity reduction of 17% with factor
β
= 450.
Conclusion
A digital
68
GaGa-DOTA-TATE PET/MR together with BSREM using factor
β
= 450 result in 17% injected activity reduction with quantitative values at least similar to analogue PET/CT, without compromising on PET/MR visual image quality and lesion detectability.
Purpose We evaluated FDG-positron emission tomography/computerized tomography for monitoring the response of pelvic lymph node metastasis to neoadjuvant chemotherapy for bladder cancer. We compared ...this to contrast enhanced computerized tomography. Materials and Methods Included in study were 19 consecutive patients with lymph node positive bladder cancer who underwent FDG-positron emission tomography/computerized tomography and contrast enhanced computerized tomography before and after a median of 4 cycles (range 2 to 4) of neoadjuvant chemotherapy between September 2011 and April 2012. Metabolic response was assessed according to EORTC (European Organisation for Research and Treatment of Cancer) recommendations based on the change in FDG uptake on FDG-positron emission tomography/computerized tomography. Radiological response was assessed on contrast enhanced computerized tomography according to RECIST (Response Evaluation Criteria in Solid Tumors) 1.1. All patients underwent pelvic lymph node dissection. Histopathological evaluation served as the gold standard for the nodal response. Results Before neoadjuvant chemotherapy, hypermetabolic FDG uptake was seen in all 19 patients, which matched the lymph node metastasis. Evaluating the nodal response with positron emission tomography/computerized tomography was feasible in all patients. On histopathology 16 patients were responders, including 14 with a complete pathological response of the lymph nodes. Positron emission tomography/computerized tomography and contrast enhanced computerized tomography correctly distinguished responders from nonresponders (18 of 19 patients or 94.7% and 15 of 19 or 78.9%) and complete responders from patients with residual disease (13 of 19 or 68.4% and 12 of 19 or 63.2%, respectively). Conclusions Although no definitive conclusions can be drawn from these preliminary data, positron emission tomography/computerized tomography appears feasible for evaluating the nodal response to neoadjuvant chemotherapy and distinguishing responders from nonresponders.
Purpose
Respiratory-induced motion of oesophageal tumours and lymph nodes can influence positron-emission tomography/computed tomography (PET/CT). The aim was to compare standard three-dimensional ...(3D) and motion-compensated PET/CT regarding standardized uptake value (SUV), metabolic tumour volume (MTV) and detection of lymph node metastases.
Methods
This prospective observational study (NCT02424864) included 37 newly diagnosed oesophageal cancer patients. Diagnostic PET/CT was reconstructed in 3D and motion-compensated PET/CT. MTVs of the primary tumour were calculated using an automated region-growing algorithm with SUV thresholds of 2.5 (MTV2.5) and ≥ 50% of SUVmax (MTV50%). Blinded for reconstruction method, a nuclear medicine physician assessed all lymph nodes showing
18
F‑fluorodeoxyglucose uptake for their degree of suspicion.
Results
The mean (95% CI) SUVmax of the primary tumour was 13.1 (10.6–15.5) versus 13.0 (10.4–15.6) for 3D and motion-compensated PET/CT, respectively. MTVs were also similar between the two techniques. Bland–Altman analysis showed mean differences between both measurements (95% limits of agreement) of 0.08 (−3.60–3.75), −0.26 (−2.34–1.82), 4.66 (−29.61–38.92) cm
3
and −0.95 (−19.9–18.0) cm
3
for tumour SUVmax, lymph node SUVmax, MTV2.5 and MTV50%, respectively. Lymph nodes were classified as highly suspicious (30/34 nodes), suspicious (20/22) and dubious (66/59) for metastases on 3D/motion-compensated PET/CT. No additional lymph node metastases were found on motion-compensated PET/CT. SUVmax of the most intense lymph nodes was similar for both scans: mean (95% CI) 6.6 (4.3–8.8) and 6.8 (4.5–9.1) for 3D and motion-compensated, respectively.
Conclusion
SUVmax of the primary oesophageal tumour and lymph nodes was comparable on 3D and motion-compensated PET/CT. The use of motion-compensated PET/CT did not improve lymph node detection.
Our hypothesis was that pretreatment inflammation in the lung makes pulmonary tissue more susceptible to radiation damage. The relationship between pretreatment (18)Ffluorodeoxyglucose ((18)FFDG) ...uptake in the lungs (as a surrogate for inflammation) and the delivered radiation dose and radiation-induced lung toxicity (RILT) was investigated.
We retrospectively studied a prospectively obtained cohort of 101 non-small-cell lung cancer patients treated with (chemo)radiation therapy (RT). (18)FFDG-positron emission tomography-computed tomography (PET-CT) scans used for treatment planning were studied. Different parameters were used to describe (18)FFDG uptake patterns in the lungs, excluding clinical target volumes, and the interaction with radiation dose. An increase in the dyspnea grade of 1 (Common Terminology Criteria for Adverse Events version 3.0) or more points compared to the pre-RT score was used as an endpoint for analysis of RILT. The effect of (18)FFDG and CT-based variables, dose, and other patient or treatment characteristics that effected RILT was studied using logistic regression.
Increased lung density and pretreatment (18)FFDG uptake were related to RILT after RT with univariable logistic regression. The 95th percentile of the (18)FFDG uptake in the lungs remained significant in multivariable logistic regression (p = 0.016; odds ratio OR = 4.3), together with age (p = 0.029; OR = 1.06), and a pre-RT dyspnea score of ≥1 (p = 0.005; OR = 0.20). Significant interaction effects were demonstrated among the 80th, 90th, and 95th percentiles and the relative lung volume receiving more than 2 and 5 Gy.
The risk of RILT increased with the 95th percentile of the (18)FFDG uptake in the lungs, excluding clinical tumor volume (OR = 4.3). The effect became more pronounced as the fraction of the 5%, 10%, and 20% highest standardized uptake value voxels that received more than 2 Gy to 5 Gy increased. Therefore, the risk of RILT may be decreased by applying sophisticated radiotherapy techniques to avoid areas in the lung with high (18)FFDG uptake.
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