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Objectives: To compare the diagnostic accuracy of (111)In-pentetreotide-scintigraphy with (68)Ga-DOTATOC-positron emission tomography (PET)/computed tomography (CT) in patients with metastatic-neuroendocrine tumour (NET) scheduled for peptide receptor radionuclide therapy (PRRT). Incremental lesions (ILs) were defined as lesions observed on only one modality.Methods: Fifty-three metastatic-NET-patients underwent (111)In-pentetreotide-scintigraphy (24 h post-injection; planar+single-photon emission CT (SPECT) abdomen) and whole-body (68)Ga-DOTATOC-PET/CT. SPECT and PET were compared in a lesion-by-lesion and organ-by-organ analysis, determining the total lesions and ILs for both modalities.Results: Significantly more lesions were detected on (68)Ga-DOTATOC-PET/CT versus (111)In-pentetreotide-scintigraphy. More specifically, we observed 1,098 lesions on PET/CT (range: 1-105; median: 15) versus 660 on SPECT (range: 0-73, median: 9) (p<0.0001), with 439 PET-ILs (42/53 patients) and one SPECT-IL (1/53 patients). The sensitivity for PET/CT was 99.9 % (95 % CI, 99.3-100.0), for SPECT 60.0 % (95 % CI, 48.5-70.2). The organ-by-organ analysis showed that the PET-ILs were most frequently visualized in liver and skeleton.Conclusion: Ga-DOTATOC-PET/CT is superior for the detection of NET-metastases compared to (111)In-pentetreotide SPECT.Key Points: Somatostatin receptor PET is superior to SPECT in detecting NET metastases. PET is the scintigraphic method for accurate depiction of NET tumour burden. The sensitivity of PET is twofold higher than the sensitivity of SPECT. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the predictive value of 7-week apparent diffusion coefficient change from baseline (ADCratio 7w ) at whole-body diffusion-weighted MRI (WB-DWI MRI) after one peptide receptor radionuclide therapy (PRRT) cycle to predict outcome in patients with metastatic neuroendocrine tumor (mNET). Materials and Methods From April 2009 to May 2012, participants in a prospective clinical trial investigating yttrium 90-DOTA Phe1-Tyr 3 -octreotide (DOTATOC) treatment for mNET (EudraCT no. 2008-007965-22) underwent WB-DWI MRI and gallium 68 ( 68 Ga)-DOTATOC PET/CT before and 7 weeks after one PRRT cycle. ADCratio 7w response was compared with the 7-week Response Evaluation Criteria in Solid Tumors version 1.1 and 68 Ga-DOTATOC PET/CT quantitative responses to predict overall survival (OS) and progression-free survival (PFS) with Cox regression analysis. Results Forty participants were analyzed (mean age, 60 years ± 11 [SD]; 21 men). Median PFS and OS were 10.5 months (range, 2-36 months) and 18 months (range, 3-81 months), respectively. Survival analysis showed significantly positive effects on PFS by age (hazard ratio [HR] = 0.96, P = .007), tumor grade (HR = 2.84, P = .006), Ki-67 index (HR = 1.05, P = .01), ADCratio 7w of the least-responding lesion (ADCratio 7w-least ) (HR = 0.94, P < .001), and baseline mean standardized uptake values (SUV mean ) (HR = 0.89, P = .02), with ADCratio 7w-least and SUV mean remaining significant in multivariable analysis ( P < .001, P = .02, respectively). There were significantly positive effects on OS by pretreatment lesion volume (HR = 1.004, P = .004), tumor grade (HR = 2.14, P = .04), Ki-67 index (HR = 1.05, P = .01), and ADCratio 7w-least (HR = 0.97, P < .001), with pretreatment volume and ADCratio 7w-least remaining significant at multivariable analysis ( P = .005, P = .002, respectively). Conclusion The ADCratio 7w after start of PRRT for mNET was an independent predictor of patient outcome. Keywords: MR-Diffusion-Weighted Imaging, Radionuclide Therapy, Whole-Body Imaging, Metastases, Tumor Response, Treatment Effects EudraCT no. 2008-007965-22 © RSNA, 2022.

We performed post hoc analyses on the utility of pretherapeutic and early interim 68 Ga-DOTATOC PET tumor uptake and volumetric parameters and a recently proposed biomarker, the inflammation-based index (IBI), for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumor (NET) patients treated with 90 Y-DOTATOC in the setting of a prospective phase II trial. Methods: Forty-three NET patients received up to 4 cycles of 90 Y-DOTATOC at 1.85 GBq/m 2 /cycle with a maximal kidney biologic effective dose of 37 Gy. All patients underwent 68 Ga-DOTATOC PET/CT at baseline and 7 wk after the first PRRT cycle. 68 Ga-DOTATOC-avid tumor lesions were semiautomatically delineated using a customized SUV threshold-based approach. PRRT response was assessed on CT using RECIST 1.1. Results: Median progression-free survival and overall survival (OS) were 13.9 and 22.3 mo, respectively. An SUV mean higher than 13.7 (75th percentile) was associated with better survival (hazard ratio [HR], 0.45; P = 0.024), whereas a 68 Ga-DOTATOC-avid tumor volume higher than 578 cm 3 (75th percentile) was associated with worse OS (HR, 2.18; P = 0.037). Elevated baseline IBI was associated with worse OS (HR, 3.90; P = 0.001). Multivariate analysis corroborated independent associations between OS and SUV mean ( P = 0.016) and IBI ( P = 0.015). No significant correlations with progression-free survival were found. A composite score based on SUV mean and IBI allowed us to further stratify patients into 3 categories with significantly different survival. On early interim PET, a decrease in SUV mean of more than 17% (75th percentile) was associated with worse survival (HR, 2.29; P = 0.024). Conclusion: Normal baseline IBI and high 68 Ga-DOTATOC tumor uptake predict better outcome in NET patients treated with 90 Y-DOTATOC. This method can be used for treatment personalization. Interim 68 Ga-DOTATOC PET does not provide information for treatment personalization., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: To investigate the relationship between the dynamic parameters (Ki) and static image-derived parameters of 68Ga-DOTATOC-PET, to determine which static parameter best reflects underlying somatostatin-receptor-expression (SSR) levels on neuroendocrine tumours (NETs)., Patients, Methods: 20 patients with metastasized NETs underwent a dynamic and static 68Ga-DOTATOC-PET before PRRT and at 7 and 40 weeks after the first administration of 90Y-DOTATOC (in total 4 cycles were planned); 175 lesions were defined and analyzed on the dynamic as well as static scans. Quantitative analysis was performed using the software PMOD. One to five target lesions per patient were chosen and delineated manually on the baseline dynamic scan and further, on the corresponding static 68Ga-DOTATOC-PET and the dynamic and static 68Ga-DOTATOC-PET at the other time-points; SUVmax and SUVmean of the lesions was assessed on the other six scans. The input function was retrieved from the abdominal aorta on the images. Further on, Ki was calculated using the Patlak-Plot. At last, 5 reference regions for normalization of SUVtumour were delineated on the static scans resulting in 5 ratios (SUVratio)., Results: SUVmax and SUVmean of the tumoural lesions on the dynamic 68Ga-DOTATOC-PET had a very strong correlation with the corresponding parameters in the static scan (R²: 0.94 and 0.95 respectively). SUVmax, SUVmean and Ki of the lesions showed a good linear correlation; the SUVratios correlated poorly with Ki. A significantly better correlation was noticed between Ki and SUVtumour(max and mean) (p < 0.0001)., Conclusions: As the dynamic parameter Ki correlates best with the absolute SUVtumour, SUVtumour best reflects underlying SSR-levels in NETs.

Purpose: Assessment of kidney function evolution after (90)Y-DOTATOC peptide receptor radionuclide therapy (PRRT) with capped activity administration based on a 37-Gy threshold of biological effective dose (BED) to the kidney., Methods: In a prospective phase II study, patients with metastasized neuroendocrine tumours were evaluated for therapy using 185 MBq (111)In-pentetreotide with amino acid coinfusion. Planar whole-body images were acquired at four time-points after injection and kidney volumes were measured using CT/MRI. BED to the kidneys was estimated using an extended BED formula and biexponential renal clearance. Based on published BED dose-toxicity relationships, we allowed a maximal kidney BED of 37 Gy; if the calculated BED exceeded 37 Gy, treatment activity was reduced accordingly. Kidney function was assessed at baseline and at 18 months, predominantly using (51)Cr-EDTA. The rate of renal function decline was expressed as annual glomerular filtration rate loss (aGFRL)., Results: Only 22 of 50 patients reached the 18-months time-point, with most missing patients having died due to disease progression. In the 22 patients who reached 18 months, no rapid kidney function deterioration was observed over the 18 months, aGFRL >33% was not seen, and only three patients showed an increase of one toxicity grade and one patient an increase of two grades. No significant correlations between kidney volume (p = 0.35), baseline GFR (p = 0.18), risk factors for renal function loss (p = 0.74) and aGFRL were observed. Among the 28 patients who did not reach 18 months, one developed grade 4 kidney toxicity at 15 months after PRRT., Conclusion: Prospective dosimetry using a 37 Gy BED as the threshold for kidney toxicity is a good guide for (90)Y-DOTATOC PRRT and is associated with a low risk of rapid renal function deterioration and evolution to severe nephrotoxicity.

Peptide receptor radionuclide therapy (PRRT), with (90)Y-DOTATOC and (177)Lu-DOTATATE as most clinically used radiopeptides, is widely used in the management of metastatic neuroendocrine tumors. With respect to radiation dosimetry, the kidneys are the critical organ for (90)Y-DOTATOC. Renal irradiation is significant because of reabsorption of the radiopeptide from the proximal tubuli and the resulting retention in the interstitium, mainly in the inner cortical zone. The high energy and consequently wide range in tissue of the yttrium-90 beta particle result in high absorbed doses to the kidney cortex and medulla. Accurate renal dosimetry can help minimizing radiation nephropathy. We report a case of a 69-year-old candidate for PRRT with an acceptable kidney function at the time of screening. When performing (111)In-octreotide pretreatment dosimetry 3 weeks later, we observed a drastic deterioration in kidney function, caused by undisclosed non-steroidal anti-inflammatory drug intake. The calculated kidney biological effective dose (BED) was 153 Gy after four projected cycles. PRRT was canceled as our full-course BED limit is 37 Gy and the patient was switched to morphine analgesics. Renal function normalized after 3 months and repeated dosimetry yielded an acceptable kidney BED of 28 Gy after four projected cycles (7 Gy/cycle). This case emphasizes that acute kidney insufficiency can yield toxic kidney doses in a single therapy cycle, with an inherent risk of persistent renal insufficiency. All clinical factors which might influence kidney function should be verified at screening and before PRRT administration.

Neuroendocrine tumors (NET) have several distinct pathophysiological features that can be addressed by specific radiolabeled probes. An overview on the different radiopharmaceuticals that have been developed for positron emission tomography (PET) of NET are presented. The focus is on fluordeoxyglucose (F-18 FDG), biogenic amine precursors, somatostatin analogs, and hormone syntheses markers. Due to the highly specific tracers lacking any clear anatomical landmarking, the advantages of integrated functional and morphological imaging systems such as PET-CT are obvious. Based on the up to now published literature and one's own experience, it is concluded that amine precursors (e.g. fluor-dihydroxyphenylalanin and hydroxytryptophane) should be employed in most gastroenteropancreatic NET, whereas F-18 FDG should be preserved for more aggressive less-differentiated NETs. Hormone syntheses markers have up to now only been used in few centers and their broad clinical value remains uncertain. The different available somatostatin analogs are the most promising tracers, since they can improve dosimetry in cases where peptide receptor radiotherapies are planned. Of specific interest are the somatostatin analogs addressing several subtypes of the somatostatin receptor (e.g. DOTANOC) that allow detecting also subtypes not expressing the "classically" addressed subtype 2 and 5. Since NET have a high variety of different features, the individual diagnostic approach using PET or integrated PET-CT should be tailored, depending on the histological classification and the differentiation of the tumor.

A 57-year-old man with an adenocarcinoma of the prostate, presented with multiple lymph nodes in the para-aortic and right iliac region on computer tomography (CT). However, since the radiologic images were taken 3 weeks following an urosepsis, the differentiation between inflamed and metastatic lymph nodes is difficult. Thus, an integrated [C] choline positron emission tomography and computer tomography (PET/CT) was performed, showing multiple lymph nodes. The patient was staged as cT3N1M0 and treated with hormonal therapy. The choline PET/CT performed after hormonal treatment showed no more hypermetabolic lymph nodes. This case substantiate the hypothesis that choline PET/CT could be used to evaluate therapy response in prostate cancer patients.