Search

The purpose of this study was to quantify any differences between the SUVs of 89 Zr immuno-PET scans obtained using a PET/CT system with a long axial field of view (LAFOV; Biograph Vision Quadra) compared to a PET/CT system with a short axial field of view (SAFOV; Biograph Vision) and to evaluate how LAFOV PET scan duration affects image noise and SUV metrics. Methods: Five metastatic breast cancer patients were scanned consecutively on SAFOV and LAFOV PET/CT scanners. Four additional patients were scanned using only LAFOV PET/CT. Scans on both systems lasted approximately 30 min and were acquired 4 d after injection of 37 MBq of 89 Zr-trastuzumab. LAFOV list-mode data were reprocessed to obtain images acquired using shorter scan durations (15, 10, 7.5, 5, and 3 min). Volumes of interest were placed in healthy tissues, and tumors were segmented semiautomatically to compare coefficients of variation and to perform Bland-Altman analysis on SUV metrics (SUV max , SUV peak , and SUV mean ). Results: Using 30-min images, 2 commonly used lesion SUV metrics were higher for SAFOV than for LAFOV PET (SUV max , 16.2% ± 13.4%, and SUV peak , 10.1% ± 7.2%), whereas the SUV mean of healthy tissues showed minimal differences (0.7% ± 5.8%). Coefficients of variation in the liver derived from 30-min SAFOV PET were between those of 3- and 5-min LAFOV PET. The smallest SUV max and SUV peak differences between SAFOV and LAFOV were found for 3-min LAFOV PET. Conclusion: LAFOV 89 Zr immuno-PET showed a lower SUV max and SUV peak than SAFOV because of lower image noise. LAFOV PET scan duration may be reduced at the expense of increasing image noise and bias in SUV metrics. Nevertheless, SUV peak showed only minimal bias when reducing scan duration from 30 to 10 min., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

In this PD-L1 ImagiNg to prediCt durvalumab treatment response in SCCHN (PINCH) study, we performed 89 Zr-DFO-durvalumab (anti-PD-L1 [programmed death ligand 1]) PET/CT in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) before monotherapy durvalumab treatment. The primary aims were to assess safety and feasibility of 89 Zr-DFO-durvalumab PET imaging and predict disease control rate during durvalumab treatment. Secondary aims were to correlate 89 Zr-DFO-durvalumab uptake to tumor PD-L1 expression, 18 F-FDG uptake, and treatment response of individual lesions. Methods: In this prospective multicenter phase I-II study (NCT03829007), patients with incurable R/M SCCHN underwent baseline 18 F-FDG PET and CT or MRI. Subsequently, PD-L1 PET imaging was performed 5 d after administration of 37 MBq of 89 Zr-DFO-durvalumab. To optimize imaging conditions, dose finding was performed in the first 14 patients. For all patients ( n = 33), durvalumab treatment (1,500 mg/4 wk, intravenously) was started within 1 wk after PD-L1 PET imaging and continued until disease progression or unacceptable toxicity (maximum, 24 mo). CT evaluation was assessed according to RECIST 1.1 every 8 wk. PD-L1 expression was determined by combined positive score on (archival) tumor tissue. 89 Zr-DFO-durvalumab uptake was measured in 18 F-FDG-positive lesions, primary and secondary lymphoid organs, and blood pool. Results: In total, 33 patients with locoregional recurrent ( n = 12) or metastatic SCCHN ( n = 21) were enrolled. 89 Zr-DFO-durvalumab injection was safe. A dose of 10 mg of durvalumab resulted in highest tumor-to-blood ratios. After a median follow-up of 12.6 mo, overall response rate was 26%. The disease control rate at 16 wk was 48%, with a mean duration of 7.8 mo (range, 1.7-21.1). On a patient level, 89 Zr-DFO-durvalumab SUV peak or tumor-to-blood ratio could not predict treatment response (hazard ratio, 1.5 [95% CI, 0.5-3.9; P = 0.45] and 1.3 [95% CI, 0.5-3.3; P = 0.60], respectively). Also, on a lesion level, 89 Zr-DFO-durvalumab SUV peak showed no substantial correlation to treatment response (Spearman ρ, 0.45; P = 0.051). Lesional 89 Zr-DFO-durvalumab uptake did not correlate to PD-L1 combined positive score but did correlate to 18 F-FDG SUV peak (Spearman ρ, 0.391; P = 0.005). Conclusion: PINCH is the first, to our knowledge, PD-L1 PET/CT study in patients with R/M SCCHN and has shown the feasibility and safety of 89 Zr-DFO-durvalumab PET/CT in a multicenter trial. 89 Zr-DFO-durvalumab uptake did not correlate to durvalumab treatment response., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

It is unknown whether assessment of potential bone lesions in metastatic breast cancer (MBC) by 18 F-FDG PET instead of 99m Tc bone scintigraphy (BS) supports clinically relevant changes in MBC management. Therefore, we retrospectively compared management recommendations based on bone lesion assessment by 18 F-FDG PET plus contrast-enhanced CT (ceCT) or BS plus ceCT, for patients with newly diagnosed MBC. Methods: Baseline ceCT, BS, and 18 F-FDG PET for all patients included in the IMPACT-MBC study (NCT01957332) at the University Medical Center Groningen were reviewed for bone lesions. If bone lesions were found by any imaging modality, virtual MBC management recommendations were made by a multidisciplinary expert panel, based on either 18 F-FDG PET plus ceCT or BS plus ceCT. The panel had access to standard clinicopathologic information and baseline imaging findings outside the skeleton. Clinically relevant management differences between the 2 recommendations were defined either as different treatment intent (curative, noncurative, or unable to determine) or as different systemic or local treatment. If no bone lesions were found by any imaging modality, the patients were included in the analyses without expert review. Results: In total, 3,473 unequivocal bone lesions were identified in 102 evaluated patients (39% by ceCT, 26% by BS, and 87% by 18 F-FDG PET). Additional bone lesions on 18 F-FDG PET plus ceCT compared with BS plus ceCT led to change in MBC management recommendations in 16% of patients (95% CI, 10%-24%). BS also changed management compared with 18 F-FDG PET in 1 patient (1%; 95% CI, 0%-5%). In 26% (95% CI, 19%-36%) of patients, an additional 18 F-FDG PET exam was requested, because BS provided insufficient information. Conclusion: In this exploratory analysis of newly diagnosed MBC patients, 18 F-FDG PET versus BS to assess bone lesions resulted in clinically relevant management differences in 16% of patients. BS delivered insufficient information in over one fourth of patients, resulting in an additional request for 18 F-FDG PET. On the basis of these data, 18 F-FDG PET should be considered a primary imaging modality for assessment of bone lesions in newly diagnosed MBC., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Pediatric differentiated thyroid cancer (DTC) is a rare disease. Initial treatment of DTC consists of a (near) total thyroidectomy and radioactive iodine ( 131 I) therapy. Previous studies in adults showed that 131 I treatment may result in a reduced salivary gland function. Studies regarding salivary gland function in children treated for DTC are sparse. Our aim was to assess long-term effects of 131 I treatment on salivary gland function in survivors of pediatric DTC. Methods: In a nationwide cross-sectional study, salivary gland function of patients treated for pediatric DTC between 1970 and 2013 (>5 years after diagnosis, ≥18 years old at time of evaluation) was studied. Salivary gland function was assessed by sialometry, sialochemistry and a xerostomia inventory. Salivary gland dysfunction was defined as unstimulated whole saliva flow ≤0.2mL/min and/or a stimulated whole saliva flow ≤0.7 mL/min. Results: Sixty-five patients (median age at evaluation 33 [IQR, 25-40] years, 86.2% female, median follow-up period 11 [IQR, 6-22] years) underwent 131 I treatment. Median cumulative 131 I activity was 5.88 [IQR, 2.92-12.95] GBq, 47.7% underwent multiple 131 I administrations. Salivary gland dysfunction was present in 30 (47.6%) patients. Levels of amylase and total protein in saliva were reduced. Moderate to severe xerostomia was present in 22 (35.5%) patients. Stimulated salivary secretion was lower and severity of xerostomia complaints higher in patients treated with higher cumulative 131 I activity. Conclusion: In survivors of pediatric DTC, clinically significant salivary gland dysfunction was found in 35.5% and was related to the cumulative 131 I activity of the treatment., (Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Development of new oncology drugs has increased since the improved understanding of cancer's complex biology. The oncology field has become the top therapeutic research area for new drugs. However, only a limited number of drugs entering clinical trials will be approved for use as the standard of care for cancer patients. Molecular imaging is increasingly perceived as a tool to support go/no-go decisions early during drug development. It encompasses a wide range of techniques that include radiolabeling a compound of interest followed by visualization with SPECT or PET. Radiolabeling can be performed using a variety of radionuclides, which are preferably matched to the compound on the basis of size and half-life. Imaging can provide information on drug behavior in vivo, whole-body drug target visualization, and heterogeneity in drug target expression. This review focuses on current applications of molecular imaging in the development of small molecules, antibodies, and antihormonal anticancer drugs., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

In theranostics, radiolabeled compounds are used to determine a treatment strategy by combining therapeutics and diagnostics in the same agent. Monoclonal antibodies (mAbs) and antibody-related therapeutics represent a rapidly expanding group of cancer medicines. Theranostic approaches using these drugs in oncology are particularly interesting because antibodies are designed against specific targets on the tumor cell membrane and immune cells as well as targets in the tumor microenvironment. In addition, these drugs are relatively easy to radiolabel. Noninvasive molecular imaging techniques, such as SPECT and PET, provide information on the whole-body distribution of radiolabeled mAbs and antibody-related therapeutics. Molecular antibody imaging can potentially elucidate drug target expression, tracer uptake in the tumor, tumor saturation, and heterogeneity for these parameters within the tumor. These data can support drug development and may aid in patient stratification and monitoring of the treatment response. Selecting a radionuclide for theranostic purposes generally starts by matching the serum half-life of the mAb or antibody-related therapeutic and the physical half-life of the radionuclide. Furthermore, PET imaging allows better quantification than the SPECT technique. This information has increased interest in theranostics using PET radionuclides with a relatively long physical half-life, such as 89 Zr. In this review, we provide an overview of ongoing research on mAbs and antibody-related theranostics in preclinical and clinical oncologic settings. We identified 24 antibodies or antibody-related therapeutics labeled with PET radionuclides for theranostic purposes in patients. For this approach to become integrated in standard care, further standardization with respect to the procedures involved is required., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Currently, biomarkers that predict the efficacy of everolimus in metastatic renal cell carcinoma (mRCC) patients are lacking. Everolimus inhibits vascular endothelial growth factor A (VEGF-A) expression. We performed PET scans on mRCC patients with 89 Zr-bevacizumab, a VEGF-A-binding antibody tracer. The aims were to determine a change in tumor tracer uptake after the start of everolimus and to explore whether 89 Zr-bevacizumab PET can identify patients with early disease progression. Methods: 89 Zr-bevacizumab PET was done before and 2 and 6 wk after the start of everolimus, 10 mg/d, in mRCC patients. Routine CT scans were performed at baseline and every 3 mo thereafter. Tumor tracer uptake was quantified using SUV max The endpoints were a change in tumor tracer uptake and treatment response on CT after 3 mo. Results: Thirteen patients participated. The median SUV max of 94 tumor lesions was 7.3 (range, 1.6-59.5). Between patients, median tumor SUV max varied up to 8-fold. After 2 wk, median SUV max was 6.3 (1.7-62.3), corresponding to a mean decrease of 9.1% ( P < 0.0001). Three patients discontinued everolimus early. At 6 wk, a mean decrease in SUV max of 23.4% compared with baseline was found in 70 evaluable lesions of 10 patients, with a median SUV max of 5.4 (1.1-49.4, P < 0.0001). All 10 patients who continued treatment had stable disease at 3 mo. Conclusion: Everolimus decreases 89 Zr-bevacizumab tumor uptake. Further studies are warranted to evaluate the predictive value of 89 Zr-bevacizumab PET for everolimus antitumor efficacy., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Complaints of a dry mouth (xerostomia) and sialoadenitis are frequent side effects of radioiodine treatment in differentiated thyroid cancer (DTC) patients. However, detailed prospective data on alterations in salivary gland functioning after radioiodine treatment ( 131 I) are scarce. Therefore, the primary aim of this study was to prospectively assess the effect of high-activity radioiodine treatment on stimulated whole saliva flow rate. Secondary aims were to study unstimulated whole and stimulated glandular (i.e., parotid and submandibular) saliva flow rate and composition alterations, development of xerostomia, characteristics of patients at risk for salivary gland dysfunction, and whether radioiodine uptake in salivary glands on diagnostic scans correlates to flow rate alterations., Methods: In a multicenter prospective study, whole and glandular saliva were collected both before and 5 mo after radioiodine treatment. Furthermore, patients completed the validated xerostomia inventory. Alterations in salivary flow rate, composition, and xerostomia inventory score were analyzed. Salivary gland radioiodine uptake on diagnostic scans was correlated with saliva flow rate changes after radioiodine treatment., Results: Sixty-seven patients (mean age ± SD, 48 ± 17 y; 63% women, 84% underwent ablation therapy) completed both study visits. Stimulated whole saliva flow rate decreased after ablation therapy (from 0.92 [interquartile range, 0.74-1.25] to 0.80 [interquartile range, 0.58-1.18] mL/min, P = 0.003), as well as unstimulated whole- and stimulated glandular flow rates (P < 0.05). The concentration of salivary electrolytes was similar at both study visits, whereas the output of proteins, especially amylase (P < 0.05), was decreased. The subjective feeling of dry mouth increased (P = 0.001). Alterations in saliva flow rate were not associated with semiquantitatively assessed radioiodine uptake in salivary glands on diagnostic scans. For the small cohort of patients undergoing repeated radioiodine therapy, we could not demonstrate alterations in salivary parameters., Conclusion: We prospectively showed that salivary gland function is affected after high-activity radioiodine ablation therapy in patients with DTC. Therefore, more emphasis should be placed on salivary gland dysfunction during follow-up for DTC patients receiving high-activity radioiodine treatment., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: Patients with von Hippel-Lindau disease (VHL) are at risk to develop multiple tumors. The growth of lesions is unpredictable, and regular surveillance is critical for early treatment to control local damage. Vascular endothelial growth factor A (VEGF-A) produced locally is supposed to play an important role in development of disease manifestations and is a target for antiangiogenic therapy with the monoclonal antibody bevacizumab. We aimed to assess whether VHL manifestations can be visualized with (89)Zr-bevacizumab PET and to explore whether (89)Zr-bevacizumab PET can differentiate progressive from nonprogressive lesions., Methods: VHL patients with at least 1 measurable hemangioblastoma were eligible. (89)Zr-bevacizumab (37 MBq) was administered intravenously 4 d before the scan. Maximum standardized uptake values were calculated. PET scans were fused with routine MRI of the central nervous system and abdominal MRI or CT. Progressive lesions were defined as new lesions, lesions that became symptomatic, and lesions ≥ 10 mm that increased ≥ 10% and ≥ 4 mm on repeated anatomic imaging within 12 mo., Results: Twenty-two patients were enrolled. At baseline, anatomic imaging showed 311 lesions. (89)Zr-bevacizumab PET visualized 59 VHL manifestations, 0-17 per patient. The median of maximum standardized uptake values was 8.5 (range, 1.3-35.8). The detection rate for lesions ≥ 10 mm was 30.8%. Seven additional hotspots without substrate on baseline anatomic imaging were found; 2 were also detected with anatomic imaging during follow-up. Nine of 25 progressive lesions were visible on PET and 27 of 175 nonprogressive lesions, corresponding to a positive predictive value of 25% and a negative predictive value of 90%. SUVmax was similar in progressive and nonprogressive lesions (median, 4.8; range, 0.9-8.9 vs. median, 6.7; range, 1.3-35.8, P = 0.14)., Conclusion: VHL manifestations can be visualized with (89)Zr-bevacizumab PET with a striking heterogeneity in tracer accumulation. (89)Zr-bevacizumab uptake does not predict progression within 12 mo. In one third of the lesions, the drug target VEGF is available and accessible. (89)Zr-bevacizumab PET might offer a tool to select VHL patients for anti-VEGF therapy., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: Patients with suspected recurrence from differentiated thyroid carcinoma, based on an increased thyroglobulin (Tg) level and negative neck ultrasound (US), pose a clinical dilemma. Because standard imaging has a low yield identifying potential recurrence, blind (131)I treatment is often applied. However, a tumor-negative (131)I whole-body scintigraphy (WBS) prevails in 38%-50% of patients. We performed a prospective multicenter observational cohort study to test the hypothesis that (124)I PET/CT can identify the patients with a tumor-negative posttherapy (131)I WBS., Methods: Our study was designed to include 100 patients with detectable Tg and a negative neck US, who were planned for blind (131)I therapy. All patients underwent (124)I PET/CT after administration of recombinant human thyroid-stimulating hormone. Subsequently, after 4-6 wk of thyroid hormone withdrawal patients were treated with 5.5-7.4 GBq of (131)I, followed by WBS a week later. The primary endpoint was the number of (131)I therapies that could have been omitted using the predicted outcome of the (124)I PET/CT, operationalized as the concordance of tumor detection by (124)I PET/CT, using post-(131)I therapy WBS as the reference test. The study would be terminated if 3 patients had a negative (124)I PET/CT and a positive posttherapy (131)I scan., Results: After inclusion of 17 patients, we terminated the study preliminarily because the stopping rule had been met. Median Tg level at (131)I therapy was 28 μg/L (interquartile range, 129). Eight posttherapy WBS were negative (47%), all of which were correctly predicted by negative (124)I PET/CT. Nine posttherapy WBS showed iodine-avid tumor, of which 4 also had positive (124)I PET/CT findings. Sensitivity, specificity, negative predictive value, and positive predictive value of (124)I PET/CT were 44% (confidence interval [CI], 14%-79%), 100% (CI, 63%-100%), 62% (CI, 32%-86%), and 100% (CI, 40%-100%), respectively. Implementation of (124)I PET in this setting would have led to 47% (8/17) less futile (131)I treatments, but 29% of patients (5/17) would have been denied potentially effective therapy., Conclusion: In patients with biochemical evidence of recurrent differentiated thyroid carcinoma and a tumor-negative neck US, the high false-negative rate of (124)I PET/CT after recombinant human thyroid-stimulating hormone (124)I PET/CT as implemented in this study precludes its use as a scouting procedure to prevent futile blind (131)I therapy., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: A novel synthetic approach to 6-(18)F-fluoro-3,4-dihydroxy-L-phenylalanine ((18)F-DOPA), involving the nucleophilic substitution of a diaryliodonium salt precursor with non-carrier-added (18)F-fluoride, yielded a product with a specific activity that was 3 orders of magnitude higher than the product of the conventional synthesis method, involving an electrophilic substitution of a trialkylstannane precursor with (18)F2. We performed a direct comparison of high- and low-specific-activity (18)F-DOPA in a neuroendocrine tumor model to determine whether this difference in specific activity has implications for the biologic behavior and imaging properties of (18)F-DOPA., Methods: (18)F-DOPA was produced via the novel synthesis method, yielding (18)F-DOPA-H with a high specific activity (35,050 ± 4,000 GBq/mmol). This product was compared in several experiments with conventional (18)F-DOPA-L with a low specific activity (11 ± 2 GBq/mmol). In vitro accumulation experiments with the human pancreatic neuroendocrine tumor cell line BON-1 were performed at both 0 °C and 37 °C and at 37 °C in the presence of pharmacologic inhibitors of proteins involved in the uptake mechanism of (18)F-DOPA. Small-animal PET experiments were performed in athymic nude mice bearing a BON-1 tumor xenograft., Results: At 37 °C, the uptake of both (18)F-DOPA-H and (18)F-DOPA-L did not differ significantly during a 60-min accumulation experiment in BON-1 cells. At 0 °C, the uptake of (18)F-DOPA-L was significantly decreased, whereas the lower temperature did not alter the uptake of (18)F-DOPA-H. The pharmacologic inhibitors carbidopa and tetrabenazine also revealed differential effects between the 2 types of (18)F-DOPA in the 60-min accumulation experiment. The small-animal PET experiments did not show any significant differences in distribution and metabolism of (18)F-DOPA-H and (18)F-DOPA-L in carbidopa-pretreated mice., Conclusion: The advantages of the novel synthesis of (18)F-DOPA, which relies on nucleophilic fluorination of a diaryliodonium salt precursor, lie in the simplicity of the synthesis method, compared with the conventional, electrophilic approach and in the reduced mass of administered, pharmacologically active (19)F-DOPA. (18)F-DOPA-H demonstrated comparable imaging properties in an in vivo model for neuroendocrine tumors, despite the fact that the injected mass of material was 3 orders of magnitude less than (18)F-DOPA-L., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: No validated predictive biomarkers for antiangiogenic treatment of metastatic renal cell carcinoma (mRCC) exist. Tumor vascular endothelial growth factor A (VEGF-A) level may be useful. We determined tumor uptake of (89)Zr-bevacizumab, a VEGF-A-binding PET tracer, in mRCC patients before and during antiangiogenic treatment in a pilot study., Methods: Patients underwent (89)Zr-bevacizumab PET scans at baseline and 2 and 6 wk after initiating either bevacizumab (10 mg/kg every 2 wk) with interferon-α (3-9 million IU 3 times/wk) (n = 11) or sunitinib (50 mg daily, 4 of every 6 wk) (n = 11). Standardized uptake values were compared with plasma VEGF-A and time to disease progression., Results: (89)Zr-bevacizumab PET scans visualized 125 evaluable tumor lesions in 22 patients, with a median SUV(max) (maximum standardized uptake value) of 6.9 (range, 2.3-46.9). Bevacizumab/interferon-α induced a mean change in tumor SUV(max) of -47.0% (range, -84.7 to +20.0%; P < 0.0001) at 2 wk and an additional -9.7% (range, -44.8 to +38.9%; P = 0.015) at 6 wk. In the sunitinib group, the mean change in tumor SUV(max) was -14.3% at 2 wk (range, -80.4 to +269.9; P = 0.006), but at 6 wk the mean change in tumor SUV(max) was +72.6% (range, -46.4 to +236%; P < 0.0001) above baseline. SUV(max) was not related to plasma VEGF-A at all scan moments. A baseline mean tumor SUV(max) greater than 10.0 in the 3 most intense lesions corresponded with longer time to disease progression (89.7 vs. 23.0 wk; hazard ratio, 0.22; 95% confidence interval, 0.05-1.00)., Conclusion: Tumor uptake of (89)Zr-bevacizumab is high in mRCC, with remarkable interpatient and intrapatient heterogeneity. Bevacizumab/interferon-α strongly decreases tumor uptake whereas sunitinib results in a modest reduction with an overshoot after 2 drug-free weeks. High baseline tumor SUV(max) was associated with longer time to progression., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: Everolimus increases progression-free survival in patients with advanced neuroendocrine tumors (NETs). Currently, no biomarkers are available for early selection of patients who will benefit from everolimus. Everolimus can reduce vascular endothelial growth factor A (VEGF-A) production by tumor cells. Therefore, we aimed to investigate the effect of everolimus on tumor uptake of the radioactive-labeled VEGF-A antibody bevacizumab with PET in NET patients., Methods: Patients with advanced progressive well-differentiated NETs underwent (89)Zr-bevacizumab PET scans before and at 2 and 12 wk during everolimus treatment. (89)Zr-bevacizumab uptake was quantified by the maximum standardized uptake value (SUVmax). Tumor response and the percentage change in the sum of target lesion diameters were determined according to Response Evaluation Criteria in Solid Tumors 1.1 on CT (3 monthly)., Results: In 4 of the 14 patients entered, no tumor lesions were visualized with (89)Zr-bevacizumab PET. In the remaining patients, 19% of tumor lesions 1 cm or greater known by CT were visualized. Tumor SUVmax decreased during everolimus treatment, with a median of -7% at 2 wk (P = 0.09) and a median of -35% at 12 wk (P < 0.001). The difference in SUVmax at 2 and 12 wk with respect to SUVmax at baseline correlated with percentage change on CT at 6 mo (r(2) = 0.51, P < 0.05, and r(2) = 0.61, P < 0.01, respectively)., Conclusion: This study demonstrates variable (89)Zr-bevacizumab PET tumor uptake in NET patients. (89)Zr-bevacizumab tumor uptake diminished during everolimus treatment. Serial (89)Zr-bevacizumab PET might be useful as an early predictive biomarker of anti-VEGF-directed treatment in NET patients., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: Vascular endothelial growth factor (VEGF)-A is overexpressed in most malignant and premalignant breast lesions. VEGF-A can be visualized noninvasively with PET imaging and using the tracer (89)Zr-labeled bevacizumab. In this clinical feasibility study, we assessed whether VEGF-A in primary breast cancer can be visualized by (89)Zr-bevacizumab PET., Methods: Before surgery, breast cancer patients underwent a PET/CT scan of the breasts and axillary regions 4 d after intravenous administration of 37 MBq of (89)Zr-bevacizumab per 5 mg. PET images were compared with standard imaging modalities. (89)Zr-bevacizumab uptake was quantified as the maximum standardized uptake value (SUV max). VEGF-A levels in tumor and normal breast tissues were assessed with enzyme-linked immunosorbent assay. Data are presented as mean ± SD., Results: Twenty-five of 26 breast tumors (mean size ± SD, 25.1 ± 19.8 mm; range, 4-80 mm) in 23 patients were visualized. SUV max was higher in tumors (1.85 ± 1.22; range, 0.52-5.64) than in normal breasts (0.59 ± 0.37; range, 0.27-1.69; P < 0.001). The only tumor not detected on PET was 10 mm in diameter. Lymph node metastases were present in 10 axillary regions; 4 could be detected with PET (SUV max, 2.66 ± 2.03; range, 1.32-5.68). VEGF-A levels in the 17 assessable tumors were higher than in normal breast tissue in all cases (VEGF-A/mg protein, 184 ± 169 pg vs. 10 ± 21 pg; P = 0.001), whereas (89)Zr-bevacizumab tumor uptake correlated with VEGF-A tumor levels (r = 0.49)., Conclusion: VEGF-A in primary breast cancer can be visualized by means of (89)Zr-bevacizumab PET.

Unlabelled: The transition from stable to progressive disease is unpredictable in patients with biochemical evidence of medullary thyroid carcinoma (MTC). Calcitonin and carcinoembryonic antigen (CEA) doubling times are currently the most reliable markers for progression, but for accurate determination, serial measurements, which need time, are required. We compared (18)F-FDG PET and (18)F-dihydroxyphenylanaline ((18)F-DOPA) PET with biochemical parameters and survival to assess whether these imaging modalities could be of value in detecting progressive disease., Methods: We evaluated the outcome of (18)F-FDG PET or (18)F-DOPA PET with calcitonin and CEA doubling times in 47 MTC patients. A subgroup of patients was included in the whole metabolic burden (WBMTB) analysis, with determination of standardized uptake values and number of lesions. WBMTB of (18)F-DOPA PET and (18)F-FDG PET was compared with biochemical parameters. Furthermore, survival was compared with (18)F-DOPA PET or (18)F-FDG PET positivity., Results: Doubling times were available for 38 of 40 patients undergoing (18)F-FDG PET. There was a significant correlation with (18)F-FDG PET positivity. Doubling times were less than 24 mo in 77% (n = 10/13) of (18)F-FDG PET-positive patients, whereas 88% (n = 22/25) of (18)F-FDG PET-negative patients had doubling times greater than 24 mo (P < 0.001). Between doubling times and (18)F-DOPA PET positivity, no significant correlation existed. (18)F-DOPA PET detected significantly more lesions (75%, 56/75) than did (18)F-FDG PET (47%, 35/75) in the 21 patients included in WBMTB analysis (P = 0.009). Calcitonin and CEA levels correlated significantly with WBMTB on (18)F-DOPA PET, but doubling times did not. (18)F-FDG PET positivity was a more important indicator for poor survival in patients for whom both scans were obtained., Conclusion: (18)F-FDG PET is superior in detecting patients with biochemical progressive disease and identifying patients with poor survival. Although (18)F-DOPA PET has less prognostic value, it can more accurately assess the extent of the disease in patients with residual MTC. Hence, both scans are informative about tumor localization and behavior. On the basis of these results, we designed a clinical flow diagram for general practice in detecting recurrent MTC.

Unlabelled: Apc mutant (Apc(Min)) mice develop multiple adenomas in their intestines and are widely used to study colorectal carcinogenesis and chemopreventive approaches. Molecular imaging of intestinal adenomas could potentially provide noninvasive longitudinal evaluation of these lesions in living mice. Therefore, the aim of this study was to investigate the role of (18)F-FDG PET in the Apc(Min) mouse model., Methods: Apc(Min) mice (n = 8) fed a purified diet were imaged serially after injection of (18)F-FDG at age 9 and 12 wk using a small-animal PET scanner. Abdominal uptake of the tracer was quantified. After dissection, intestines were imaged separately, and intestinal tracer uptake was quantified. Tracer distribution was compared with results from microscopic examination regarding adenoma number and size. Thereafter, findings were validated serially in 20 Apc(Min) mice aged 6, 8, 10, and 12 wk that received standard chow to increase adenoma numbers. In vivo abdominal (18)F-FDG uptake was correlated with microscopy results., Results: Microscopic examination showed that the mice developed 25-35 intestinal adenomas at age 12 wk. Ex vivo (18)F-FDG PET of the dissected intestines visualized all large adenomas and most small adenomas. Ex vivo total intestinal (18)F-FDG uptake correlated with in vivo total abdominal uptake and with the number of large adenomas at age 9 and 12 wk. At 12 wk, there was a clear correlation between in vivo abdominal tracer uptake and the number of large adenomas but not the total number of lesions., Conclusion: Intestinal adenomas in Apc(Min) mice are metabolically active lesions that take up (18)F-FDG. Abdominal (18)F-FDG uptake at age 12 wk serves as a readout modality for large intestinal adenomas.

In recent years, 6-l-18F-fluorodihydroxyphenylalanine (18F-DOPA) PET has emerged as a new diagnostic tool for the imaging of neuroendocrine tumors. This application is based on the unique property of neuroendocrine tumors to produce and secrete various substances, a process that requires the uptake of metabolic precursors, which leads to the uptake of 18F-DOPA. This nonsystematic review first describes basic aspects of 18F-DOPA imaging, including radiosynthesis, factors involved in tracer uptake, and various aspects of metabolism and imaging. Subsequently, this review provides an overview of current clinical applications in neuroendocrine tumors, including carcinoid tumors, pancreatic islet cell tumors, pheochromocytoma, paraganglioma, medullary thyroid cancer, hyperinsulinism, and various other clinical entities. The application of PET/CT in carcinoid tumors has unsurpassed sensitivity. In medullary thyroid cancer, pheochromocytoma, and hyperinsulinism, results are also excellent and contribute significantly to clinical management. In the remaining conditions, the initial experience with 18F-DOPA PET indicates that it seems to be less valuable, but further study is required.

Unlabelled: Vascular endothelial growth factor (VEGF), released by tumor cells, is an important growth factor in tumor angiogenesis. The humanized monoclonal antibody bevacizumab blocks VEGF-induced tumor angiogenesis by binding, thereby neutralizing VEGF. Our aim was to develop radiolabeled bevacizumab for noninvasive in vivo VEGF visualization and quantification with the single gamma-emitting isotope 111In and the PET isotope 89Zr., Methods: Labeling, stability, and binding studies were performed. Nude mice with a human SKOV-3 ovarian tumor xenograft were injected with 89Zr-bevacizumab, 111In-bevacizumab, or human 89Zr-IgG. Human 89Zr-IgG served as an aspecific control antibody. Small-animal PET and microCT studies were obtained at 24, 72, and 168 h after injection of 89Zr-bevacizumab and 89Zr-IgG (3.5 +/- 0.5 MBq, 100 +/- 6 microg, 0.2 mL [mean +/- SD]). Small-animal PET and microCT images were fused to calculate tumor uptake and compared with ex vivo biodistribution at 168 h after injection. 89Zr- and 111In-bevacizumab ex vivo biodistribution was compared at 24, 72, and 168 h after injection (2.0 +/- 0.5 MBq each, 100 +/- 4 microg in total, 0.2 mL)., Results: Labeling efficiencies, radiochemical purity, stability, and binding properties were optimal for the radioimmunoconjugates. Small-animal PET showed uptake in well-perfused organs at 24 h and clear tumor localization from 72 h onward. Tumor uptake determined by quantification of small-animal PET images was higher for 89Zr-bevacizumab-namely, 7.38 +/- 2.06 %ID/g compared with 3.39 +/- 1.16 %ID/g (percentage injected dose per gram) for human 89Zr-IgG (P = 0.011) at 168 h and equivalent to ex vivo biodistribution studies. Tracer uptake in other organs was seen primarily in liver and spleen. 89Zr- and 111In-bevacizumab biodistribution was comparable., Conclusion: Radiolabeled bevacizumab showed higher uptake compared with radiolabeled human IgG in a human SKOV-3 ovarian tumor xenograft. Noninvasive quantitative small-animal PET was similar to invasive ex vivo biodistribution. Radiolabeled bevacizumab is a new tracer for noninvasive in vivo imaging of VEGF in the tumor microenvironment.

A carcinoid crisis is a severe complication of the carcinoid syndrome that can arise in patients with advanced metastatic neuroendocrine tumors. It can be initiated by stress, catecholamines, and tumor manipulation. In this article, we report a case in which an injection with the catecholamine tracer 6-18F-fluorodihydroxyphenylalanine, used for PET, induced a carcinoid crisis. Octreotide can be used for treatment and should be available. Tracer injection should be slow.

Unlabelled: Radioimmunotherapy (RIT) can be performed with various radionuclides. We tested the stability, biodistribution, and therapeutic efficacy of various radioimmunoconjugates ((131)I, (88/90)Y, (177)Lu, and (186)Re) of chimeric antirenal cell cancer monoclonal antibody G250 (mAb cG250) in nude mice with subcutaneous renal cell cancer (RCC) tumors., Methods: The (88/90)Y and (177)Lu labeling procedures of cG250 conjugated with cyclic diethylenetriaminepentaacetic acid anhydride (cDTPA), isothiocyanatobenzyl-DTPA (SCN-Bz-DTPA), or 1,4,7,10-tetraazacyclododecanetetraacetic acid (DOTA) were characterized. Stability of the labeled conjugates in plasma at 37 degrees C was assessed. Biodistribution and therapeutic efficacy of labeled cG250 were compared in nude mice with SK-RC-52 human RCC xenografts., Results: Both SCN-Bz-DTPA and DOTA were stable in vitro (<5% release of the radiolabel during 14 and 21 d of incubation) and in vivo (uptake in bone