Differentiation of prostate cancer and benign prostatic hyperplasia: the clinical value of<Superscript>201</Superscript>Tl SPECT—A pilot study

PURPOSE: Thallium-201 (201Tl) is a recognized tumor-imaging agent; however, the usefulness of 201Tl in prostate cancer has not been studied. The purpose of this preliminary study was to evaluate the efficacy of 201Tl single-photon emission computed tomography (SPECT) imaging for differentiating prostate cancer from benign prostatic hyperplasia (BPH). METHODS: 201Tl pelvic SPECT was performed in 10 patients (aged 64-78 years) with biopsy-proven BPH before transurethral resection of the prostate and 15 patients (aged 65-81 years) with biopsy-proven prostate cancer prior to any therapeutic modality or invasive surgical procedures for treatment of their prostate cancer. RESULTS: From the 15 patients with prostate cancer, 201Tl pelvic SPECT detected prostate cancer in 13 (86.7%) but not in 2 (13.3%) patients with Gleason scores of 5 (2 + 3). In contrast, all 10 patients with BPH (100.0%) had negative results of 201Tl pelvic SPECT. CONCLUSION: Our study showed that 201Tl pelvic SPECT scan is very helpful in distinguishing between prostate cancer and BPH.     

<Superscript>125</Superscript>I brachytherapy in younger prostate cancer patients

Purpose

To evaluate local recurrence in younger men treated with low-dose-rate (LDR) ¹²⁵I brachytherapy (BT) for localized prostate cancer.

Patients and methods

A total of 192 patients (≤65-years-old) were treated with LDR ¹²⁵I-BT ± hormone therapy. Local failure was defined as any prostate-specific antigen (PSA) rise leading to salvage treatment or biochemical failure according to the Phoenix definition. A bounce was defined as a rise in the nadir of ≥0.2?ng/mL followed by spontaneous return. Proportions were compared using Fisher’s exact tests; continuous variables using the unpaired t-test or its non-parametric equivalent. Cox proportional hazards models were applied for multivariable survival analysis.

Results

Median follow-up was 66 months. The 5?year local recurrence-free survival was 96.1%. Biopsy-proven local recurrence developed in 13 patients, 4 had a Phoenix-defined recurrence at the last follow-up. Androgen deprivation therapy was started in 1 patient without proven recurrence. Univariable risk factors for local recurrence were: at least 50% positive biopsies, intermediate risk, treatment with neoadjuvant hormone therapy, low preimplantation volume receiving 100% of the prescribed dose, and no bounce development. Hormone-naïve patients not attaining a PSA value <0.5?ng/mL during follow-up also had a higher risk of local recurrences. Cox regression demonstrated that the variables “at least 50% positive biopsies” and “bounce” significantly impacted local failure (hazard ratio, HR 1.02 and 11.59, respectively). A bounce developed in 70 patients (36%). Younger patients and those treated with a lower activity per volume had a higher chance of developing a bounce in the Cox model (HR 0.99 and 0.04, respectively).

Conclusion

For younger men, LDR BT is a valid primary curative treatment option in low-risk and is to consider in intermediate-risk localized prostate cancer.

     

Detection of bone metastases in patients with prostate cancer by <Superscript>18</Superscript>F fluorocholine and <Superscript>18</Superscript>F fluoride PET–CT: a comparative study

Purpose  The aim of this prospective study was to compare the potential value of ¹⁸F fluorocholine (FCH) and ¹⁸F fluoride positron emission tomography (PET)–CT scanning for the detection of bony metastases from prostate cancer. Methods  Thirty-eight men (mean age, 69 ± 8 years) with biopsy-proven prostate cancer underwent both imaging modalities within a maximum interval of 2 weeks. Seventeen patients were evaluated preoperatively, and 21 patients were referred for post-operative evaluation of suspected recurrence or progression based on clinical algorithms. The number, sites and morphological patterns of bone lesions on ¹⁸F FCH and ¹⁸F fluoride PET–CT were correlated: Concordant lesions between the two modalities with corresponding changes on CT were considered to be positive for malignancy; discordant lesions were verified by follow-up examinations. The mean follow-up interval was 9.1 months. Results  Overall, 321 lesions were evaluated in this study. In a lesion-based analysis, a relatively close agreement was found between these two imaging modalities for detection of malignant bone lesions (kappa = 0.57), as well as in a patient-based analysis (kappa = 0.76). Sixteen malignant sclerotic lesions with a high density were negative in both ¹⁸F FCH and ¹⁸F fluoride PET–CT [mean Hounsfield unit (HU), 1,148 ± 364]. There was also a significant correlation between tracer intensity by SUV and density of sclerotic lesions by HU both in ¹⁸F FCH PET–CT (r = −0.28, p < 0.006) and ¹⁸F fluoride PET–CT (r = −0.20, p < 0.05). The sensitivity, specificity and accuracy of PET–CT in the detection of bone metastases in prostate cancer was 81%, 93% and 86% for ¹⁸F fluoride, and 74% (p = 0.12), 99% (p = 0.01) and 85% for FCH, respectively. ¹⁸F FCH PET–CT led to a change in the management in two out of 38 patients due to the early detection of bone marrow metastases. ¹⁸F fluoride PET–CT identified more lesions in some patients when compared with ¹⁸F FCH PET–CT but did not change patient management. Conclusion  FCH PET–CT may be superior for the early detection (i.e. bone marrow involvement) of metastatic bone disease. In patients with FCH-negative suspicious sclerotic lesions, a second bone-seeking agent (e.g. ¹⁸F fluoride) is recommended. ¹⁸F fluoride PET–CT demonstrated a higher sensitivity than ¹⁸F FCH PET–CT, but the difference was not statistically significant. Furthermore, ¹⁸F fluoride PET could be also negative in highly dense sclerotic lesions, which presumably reflects the effect of treatment. It will be important to clarify in future studies whether these lesions are clinically relevant when compared with metabolically active bone metastases.     

Comparison of <Superscript>18</Superscript>F–FDG PET/MRI and MRI alone for whole-body staging and potential impact on therapeutic management of women with suspected recurrent pelvic cancer: a follow-up study

Purpose

To evaluate the diagnostic performance of ¹⁸F–FDG PET/MRI for whole-body staging and potential changes in therapeutic management of women with suspected recurrent pelvic cancer in comparison with MRI alone.

Methods

Seventy-one consecutive women (54?±?13 years, range: 25–80 years) with suspected recurrence of cervical (32), ovarian (26), endometrial (7), vulvar (4), and vaginal (2) cancer underwent PET/MRI including a diagnostic contrast-enhanced MRI protocol. PET/MRI and MRI datasets were separately evaluated regarding lesion count, localization, categorization (benign/malignant), and diagnostic confidence (3-point scale; 1–3) by two physicians. The reference standard was based on histopathology results and follow-up imaging. Diagnostic accuracy and proportions of malignant and benign lesions rated correctly were retrospectively compared using McNemar’s chi² test. Differences in diagnostic confidence were assessed by Wilcoxon test.

Results

Fifty-five patients showed cancer recurrence. PET/MRI correctly identified more patients with cancer recurrence than MRI alone (100% vs. 83.6%, p?<?0.01). In contrast to PET/MRI, MRI alone missed 4/15 patients with pelvic recurrence and miscategorized 8/40 patients with distant metastases as having local recurrence only. Based on the reference standard, 241 lesions were detected in the study cohort (181 malignant, 60 benign). While PET/MRI provided correct identification of 181/181 (100%) malignant lesions, MRI alone correctly identified 135/181 (74.6%) malignant lesions, which was significantly less compared to PET/MRI (p?<?0.001). PET/MRI offered superior diagnostic accuracy (99.2% vs. 79.3%, p?<?0.001) and diagnostic confidence in the categorization of malignant lesions compared with MRI alone (2.7?±?0.5 vs. 2.4?±?0.7, p?<?0.001).

Conclusion

PET/MRI demonstrates excellent diagnostic performance and outperforms MRI alone for whole-body staging of women with suspected recurrent pelvic cancer, indicating potential changes in therapy management based on evaluation of local recurrence and distant metastatic spread.

     

Do androgens control the uptake of <Superscript>18</Superscript>F-FDG, <Superscript>11</Superscript>C-choline and <Superscript>11</Superscript>C-acetate in human prostate cancer cell lines?

Purpose  

The aim of this study was to evaluate the impact of androgen ablation therapy in different prostate cancer (PCa) cell lines—reflecting different stages of the disease—on ¹⁸F-fluorodeoxyglucose (FDG), ¹¹C-choline and ¹¹C-acetate uptake.     

<Superscript>18</Superscript>F–FDG-PET/CT for systemic staging of patients with newly diagnosed ER-positive and HER2-positive breast cancer

Objectives

This study assesses ¹⁸F–FDG-PET/CT for patients with newly diagnosed estrogen receptor-positive/human epidermal growth factor receptor-negative (ER+/HER2-) and human epidermal growth factor receptor-positive (HER2+) breast cancer.

Methods

In this Institutional Review Board-approved retrospective study, our Healthcare Information System was screened for patients with ER+/HER2- and HER2+ breast cancer who underwent ¹⁸F–FDG-PET/CT prior to systemic or radiation therapy. The initial stage was determined from mammography, ultrasound, magnetic resonance imaging, and/or surgery.¹⁸F–FDG-PET/CT was evaluated to identify unsuspected extra-axillary regional nodal and distant metastases. The proportion of patients upstaged overall and stratified by stage and receptor phenotypes was calculated along with confidence intervals (CI).

Results

A total of 238 patients with ER+/HER2- and 245 patients with HER2+ who met inclusion criteria were evaluated. For patients with ER+/HER2-breast cancer, ¹⁸F–FDG-PET/CT revealed unsuspected distant metastases in 3/71 (4%) initial stage IIA, 13/95 (14%) stage IIB, and 15/57 (26%) stage III. For patients with HER2+ breast cancer, ¹⁸F–FDG-PET/CT revealed unsuspected distant metastases in 3/72 (4%) initial stage IIA, 13/93 (14%) stage IIB, and 13/59 (22%) stage III. The overall upstaging rate for IIB was 14% (95% confidence interval (CI): 9–20%).

Conclusions

¹⁸F–FDG-PET/CT revealed distant metastases in 14% (95% CI: 9–20%) of patients with stage IIB ER+/HER2- and HER2+ breast cancer, which is similar to upstaging rates previously seen in patients with stage IIB triple-negative breast cancer (15%, 95% CI: 9–24%). The detection of unsuspected distant metastases in these patients alters treatment and prognosis. NCCN guidelines should consider adding patients with stage IIB breast cancer for consideration of systemic staging with ¹⁸F–FDG-PET/CT at the time of initial diagnosis.

     

1-[<Superscript>11</Superscript>C]-acetate PET imaging in head and neck cancer—a comparison with <Superscript>18</Superscript>F-FDG-PET: implications for staging and radiotherapy planning

Purpose The aim of this study was to evaluate the feasibility of using 1-[¹¹C]-acetate positron emission tomography (ACE-PET) to detect and delineate the gross tumour volume of head and neck cancer before radiotherapy, and to compare the results with those obtained using ¹⁸F-fluoro-2-deoxy-D-glucose (FDG) PET. Methods Ten patients with histologically verified squamous cell carcinoma were investigated by FDG-PET and dynamic ACE-PET prior to radiotherapy. The two scans were performed on the same day or on consecutive days, except in one patient in whom they were done 5 days apart. Diagnostic CT or MRI was performed in all patients. The image data sets were analysed both visually and semi-quantitatively. All primary tumours and metastases were delineated automatically by using the 50% threshold of maximum radioactivity corrected for background. The mean standardised uptake value (SUV) and the tumour volumes were evaluated and compared. Results All ten primary tumours were detected by ACE-PET, while nine primaries were detected by FDG-PET and CT and/or MRI. The ACE SUV tended to be lower than the FDG SUV (5.3±2.7 vs 9.6±7.0, p=0.07). The tumour volumes delineated with ACE were on average 51% larger than the FDG volumes (p<0.05). ACE-PET identified 20/21 lymph node metastases, while only 13/21 lesions were detected by FDG-PET and 16/21 lesions by CT or MRI. Conclusion ACE-PET appears promising for the staging of head and neck cancer. The biological information provided by both FDG and ACE must be carefully validated before it can be used in clinical routine for radiation treatment planning. More studies are needed to evaluate the differences in volumes and to confirm the clinical potential of both FDG and ACE-PET, especially in radiotherapy. The first two authors contributed equally to this paper.     

Biodistribution and radiation dosimetry of <Superscript>68</Superscript>Ga-PSMA HBED CC—a PSMA specific probe for PET imaging of prostate cancer

Purpose

Positron emission tomography (PET) agents targeting the prostate-specific membrane antigen (PSMA) are currently under broad clinical and scientific investigation. ⁶⁸Ga-PSMA HBED-CC constitutes the first ⁶⁸Ga-labelled PSMA-inhibitor and has evolved as a promising agent for imaging PSMA expression in vivo. The aim of this study was to evaluate the whole-body distribution and radiation dosimetry of this new probe.

Methods

Five patients with a history or high suspicion of prostate cancer were injected intravenously with a mean of 139.8?±?13.7 MBq of ⁶⁸Ga-PSMA HBED-CC (range 120–158 MBq). Four static skull to mid-thigh scans using a whole-body fully integrated PET/MR-system were performed 10 min, 60 min, 130 min, and 175 min after the tracer injection. Time-dependent changes of the injected activity per organ were determined. Mean organ-absorbed doses and effective doses (ED) were calculated using OLINDA/EXM.

Results

Injection of a standard activity of 150 MBq ⁶⁸Ga-PSMA HBED-CC resulted in a median effective dose of 2.37 mSv (Range 1.08E-02 – 2.46E-02 mSv/MBq). The urinary bladder wall (median absorbed dose 1.64E-01 mGv/MBq; range 8.76E-02 – 2.91E-01 mGv/MBq) was the critical organ, followed by the kidneys (median absorbed dose 1.21E-01 mGv/MBq; range 7.16E-02 – 1.75E-01), spleen (median absorbed dose 4.13E-02 mGv/MBq; range 1.57E-02 – 7.32E-02 mGv/MBq) and liver (median absorbed dose 2.07E-02 mGv/MBq; range 1.80E-02 – 2.57E-02 mGv/MBq). No drug-related pharmacological effects occurred.

Conclusion

The use of ⁶⁸Ga-PSMA HBED-CC results in a relatively low radiation exposure, delivering organ doses that are comparable to those of other ⁶⁸Ga-labelled PSMA-inhibitors used for PET-imaging. Total effective dose is lower than for other PET-agents used for prostate cancer imaging (e.g. ¹¹C- and ¹⁸F-Choline).

     

Patterns of failure after radical prostatectomy in prostate cancer – implications for radiation therapy planning after <Superscript>68</Superscript>Ga-PSMA-PET imaging

Background

Salvage radiotherapy (SRT) after radical prostatectomy (RPE) and lymphadenectomy (LAE) is the appropriate radiotherapy option for patients with persistent/ recurrent prostate cancer (PC). ⁶⁸Ga-PSMA-PET imaging has been shown to accurately detect PC lesions in a primary setting as well as for local recurrence or for lymph node (LN) metastases.

Objective

In this study we evaluated the patterns of recurrence after RPE in patients with PC, putting a highlight on the differentiation between sites that would have been covered by a standard radiation therapy (RT) field in consensus after the RTOG consensus and others that would have not.

Methods and materials

Thirty-one out of 83 patients (37%) with high-risk PC were the subject of our study. Information from ⁶⁸Ga-PSMA-PET imaging was used to individualize treatment plans to include suspicious lesions as well as possibly boost sites with tracer uptake in LN or the prostate bed. For evaluation, ⁶⁸Ga-PSMA-PET-positive LN were contoured in a patient dataset with a standard lymph drainage (RTOG consensus on CTV definition of pelvic lymph nodes) radiation field depicting color-coded nodes that would have been infield or outfield of that standard lymph drainage field and thereby visualizing typical patterns of failure of a “blind” radiation therapy after RPE and LAE.

Results

Compared to negative conventional imaging (CT/MRI), lesions suspicious for PC were detected in 27/31 cases (87.1%) by ⁶⁸Ga-PSMA-PET imaging, which resulted in changes to the radiation concept. There were 16/31 patients (51.6%) that received a simultaneous integrated boost (SIB) to a subarea of the prostate bed (in only three cases this dose escalation would have been planned without the additional knowledge of ⁶⁸Ga-PSMA-PET imaging) and 18/31 (58.1%) to uncommon (namely presacral, paravesical, pararectal, preacetabular and obturatoric) LN sites. Furthermore, 14 patients (45.2%) had a changed TNM staging result by means of ⁶⁸Ga-PSMA-PET imaging.

Conclusion

Compared to conventional CT or MRI staging, ⁶⁸Ga-PSMA-PET imaging detects more PC lesions and, thus, significantly influences radiation planning in recurrent prostate cancer patients enabling individually tailored treatment.

     

Hybrid <Superscript>18</Superscript>F–FDG PET/MRI might improve locoregional staging of breast cancer patients prior to neoadjuvant chemotherapy

Purpose

Our purpose in this study was to assess the added clinical value of hybrid ¹⁸F–FDG-PET/MRI compared to conventional imaging for locoregional staging in breast cancer patients undergoing neoadjuvant chemotherapy (NAC).

Methods

In this prospective study, primary invasive cT2-4 N0 or cT1-4 N+ breast cancer patients undergoing NAC were included. A PET/MRI breast protocol was performed before treatment. MR images were evaluated by a breast radiologist, blinded for PET images. PET images were evaluated by a nuclear physician. Afterwards, a combined PET/MRI report was written. PET/MRI staging was compared to conventional imaging, i.e., mammography, ultrasound and MRI. The proportion of patients with a modified treatment plan based on PET/MRI findings was analyzed.

Results

A total of 40 patients was included. PET/MRI was of added clinical value in 20.0% (8/40) of patients, changing the treatment plan in 10% and confirming the malignancy of suspicious lesions on MRI in another 10%. In seven (17.5%) patients radiotherapy fields were extended because of additional or affirmative PET/MRI findings being lymph node metastases (n = 5) and sternal bone metastases (n = 2). In one (2.5%) patient radiotherapy fields were reduced because of fewer lymph node metastases on PET/MRI compared to conventional imaging. Interestingly, all treatment changes were based on differences in number of lymph nodes suspicious for metastasis or number of distant metastasis, whereas differences in intramammary tumor extent were not observed.

Conclusion

Prior to NAC, PET/MRI shows promising results for locoregional staging compared to conventional imaging, changing the treatment plan in 10% of patients and potentially replacing PET/CT or tissue sampling in another 10% of patients.

     

PET imaging with [<Superscript>18</Superscript>F]3′-deoxy-3′-fluorothymidine for prediction of response to neoadjuvant treatment in patients with rectal cancer

Purpose Positron emission tomography (PET) using ¹⁸F-labelled 3′-deoxy-3′-fluorothymidine (FLT) was assessed for therapy monitoring in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy. Methods Ten patients with locally advanced rectal cancer were included and underwent long-course preoperative chemoradiotherapy (total dose 45 Gy, 1.8 Gy/day, concomitant 250 mg/m² 5-fluorouracil) followed by surgery. FLT-PET was performed prior to chemoradiotherapy, 2 weeks after initiation of chemoradiotherapy and preoperatively (3–4 weeks post chemoradiotherapy). FLT uptake was correlated with histopathological tumour regression and changes in T stage. Results Mean tumour FLT uptake was 4.2±1.0 SUV before therapy and decreased significantly to 2.9 ± 0.6 SUV 14 days after initiation of chemoradiotherapy (−28.6% ± 10.7%, p = 0.005). The preoperative scan showed a further decrease to 1.9 ± 0.4 SUV (−54.7% ± 7.6%, p = 0.005). However, the degree of change in FLT uptake 2 weeks after initiation and after completion of neoadjuvant therapy did not correlate with histopathological tumour regression. Conclusion FLT-PET did not seem to be a promising method for assessment of tumour response in the studied chemoradiotherapy regimen in patients with rectal cancer.     

Optimal time-point for <Superscript>68</Superscript>Ga-PSMA-11 PET/CT imaging in assessment of prostate cancer: feasibility of sterile cold-kit tracer preparation?

Purpose

In this prospective study, we evaluated the optimal time-point for ⁶⁸Ga-PSMA-11 PET/CT acquisition in the assessment of prostate cancer. We also examined, for the first time the feasibility of tracer production using a PSMA-11 sterile cold-kit in the clinical workflow of PET/CT centres.

Methods

Fifty prostate cancer patients (25 staging, 25 biochemical recurrence) were enrolled in this study. All patients received an intravenous dose of 2.0 MBq/kg body weight ⁶⁸Ga-PSMA-11 prepared using a sterile cold kit (ANMI SA, Liege, Belgium), followed by an early (20 min after injection) semi-whole-body PET/CT scan and a standard-delay (100 min after injection) abdominopelvic PET/CT scan. The detection rates with ⁶⁸Ga-PSMA-11 were compared between the two acquisitions. The pattern of physiological background activity and tumour to background ratio were also analysed.

Results

The total preparation time was reduced to 5 min using the PSMA-11 sterile cold kit, which improved the final radionuclide activity by about 30% per single ⁶⁸Ge/⁶⁸Ga generator elution. Overall, 158 pathological lesions were analysed in 45 patients (90%) suggestive of malignancy on both (early and standard-delay) ⁶⁸Ga-PSMA PET/CT images. There was a significant (p?<?0.001) increase in SUVmax on delayed images in suspicious prostates (11.6?±?8.2 to 14.8?±?1.0) and lymph nodes (LNs; 9.7?±?5.9 to 12.3?±?8.8), while bone lesions showed no significant increase (8.5?±?5.6 to 9.2?±?7.0, p?=?0.188). However, the SUVmax of suspicious lesions on early images was adequate to support the criteria for correct interpretation (mean SUVmax 9.83?±?6.7).In 26 of 157 lesions, but a decrease in SUV was seen, mostly in subcentimetre lesions in patients with multiple metastases. However, it did not affect the staging of the disease or patient management. The tumour to background ratio of primary prostate lesions and LNs showed a significant (p?<?0.001) increase from the early to the standard-delay acquisition, but no significant increase was seen in bony lesions (p?=?0.11).

Conclusion

The PSMA-11 sterile cold kit seems to be feasible for use in routine clinical practice, and it has a shorter radionuclide preparation time and is less operator-dependent than the synthesizer-based production method. In addition, early ⁶⁸Ga-PSMA-11 PET/CT imaging seems to provide a detection rate comparable with that of standard-delay imaging. Furthermore, the shorter preparation time using the ⁶⁸Ga-PSMA-11 sterile cold kit and promising value of early PET/CT scanning could allow tailoring of imaging protocols which may reduce the costs and improve the time efficiency in PET/CT centres.

     

<Superscript>99m</Superscript>Tc-Demotate 1: first data in tumour patients—results of a pilot/phase I study

Somatostatin receptor (SSTR) scintigraphy with indium-111 DTPA-octreotide has become a routine diagnostic procedure in oncology. However, it suffers some drawbacks concerning the limited availability, suboptimal imaging properties and elevated radiation burden of ¹¹¹In. We have recently been involved in the development of a new tetraamine-functionalised [Tyr³]octreotate derivative (Demotate 1) that can be easily labelled with technetium-99m at high specific activities. ^99mTc-Demotate 1 showed promising properties in preclinical studies. In this study we report on the first experience with ^99mTc-Demotate 1 in patients. Six patients (mean age 56 years) with carcinoid tumours (n=2) or endocrine pancreatic tumours (n=4) with previously positive SSTR scintigraphy were enrolled in the study. Patients were injected with 500–600 MBq ^99mTc-Demotate 1. Clinical and laboratory parameters were controlled up to 3 months p.i. Blood samples were taken at various time points up to 24 h p.i., and urine was collected up to 24 h. Whole-body images were acquired at 15–30 min, 1–2 h, 4 h and 24 h p.i. with additional single-photon emission tomography imaging at 1–4 h. Blood excretion was very rapid, with <2%ID in plasma after 1 h, and urinary excretion <20% ID after 6 h. Two patients complained of mild gastrointestinal problems and paraesthesia, but no other adverse reactions were observed. SSTR-positive tumours were rapidly visualised as early as 15 min p.i., with maximum tumour uptake (up to 19% ID) and tumour/organ ratios as early as 1 h p.i. Organs of predominant physiological uptake were the spleen and the kidneys, with no intestinal excretion detectable up to 24 h. ^99mTc-Demotate 1 detected 11 lesions while In-Oct detected ten; differences in uptake behaviour were observed in three patients. This study shows for the first time that peptides derivatised with a tetraamine ligand for labelling with ^99mTc show suitable properties for receptor imaging in patients. ^99mTc-Demotate 1 is a promising agent for the visualisation of SSTR-positive lesions in patients, allowing rapid imaging as early as 1 h p.i.; some differences are observed in pharmacokinetic behaviour compared with ¹¹¹In-DTPA-octreotide.     

Inter-heterogeneity and intra-heterogeneity of α<Subscript>v</Subscript>β<Subscript>3</Subscript> in non-small cell lung cancer and small cell lung cancer patients as revealed by <Superscript>68</Superscript>Ga-RGD<Subscript>2</Subscript> PET imaging

Purpose

Integrin α_vβ₃ is the therapeutic target of the anti-angiogenic drug cilengitide. The objective of this study was to compare α_vβ₃ levels in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients, by using the positron emission tomography (PET) tracer ⁶⁸Ga-labeled dimerized-RGD (⁶⁸Ga-RGD₂).

Methods

Thirty-one patients with pathologically confirmed lung cancer were enrolled (21 were NSCLC and 10 were SCLC). PET/CT images were acquired using ⁶⁸Ga-RGD₂.¹⁸F-FDG PET/CT images were also acquired on the consecutive day as reference. The standard uptake values (SUV) and the tumor/nontarget (T/NT) values were quantitatively compared. Expression of the angiogenesis marker α_vβ₃ in NSCLC and SCLC lesions was analyzed by immunohistochemistry.

Results

The ¹⁸F-FDG SUVmax and the SUVmean were not significantly different between NSCLC and SCLC patients. The ⁶⁸Ga-RGD₂ uptake of SCLC patients was at background levels in both SUV and T/NT measurements and was significantly lower than that of NSCLC patients. The range value of ⁶⁸Ga-RGD₂ SUVmean was 4.5 in the NSCLC group and 2.2 in the SCLC group, while the variation coefficient was 36.2% and 39.3% in NSCLC and SCLC primary lesions, respectively. Heterogeneity between primary lesions and putative distant metastases was also observed in some NSCLC cases. Immunostaining showed that α_vβ₃ integrin was expressed in the cells and neovasculature of NSCLC lesions, while SCLC samples had negative expression.

Conclusions

The uptake of ⁶⁸Ga-RGD₂ in SCLC patients is significantly lower than that in NSCLC patients, indicating a lower α_vβ₃ target level for cilengitide in SCLC. Apparent intra-tumor heterogeneities of α_vβ₃ also exist in both NSCLC and SCLC. Such inter- and intra-heterogeneity of α_vβ₃ may potentially improve current applications of α_vβ₃-targeted therapy and diagnostic imaging in lung cancer.

     

Detection of bone marrow and extramedullary involvement in patients with non-Hodgkin’s lymphoma by whole-body MRI: comparison with bone and <Superscript>67</Superscript>Ga scintigraphies

The aim of this study was to evaluate the diagnostic potential of whole-body MRI (WB-MRI) for the detection of bone marrow and extramedullary involvement in patients with non-Hodgkins lymphoma. WB-MRI, which was performed on 34 patients, consisted of the recording of T1-weighted spin-echo images and a fast STIR sequence covering the entire skeleton. The WB-MRI findings for bone marrow and extramedullary involvement were compared with those from ⁶⁷Ga and bone scintigraphies and bone marrow biopsy results. Two MRI specialists reviewed the WB-MRI results and two expert radiologists in the field of nuclear medicine reviewed the bone and ⁶⁷Ga scintigraphy findings. Bone marrow and extramedullary involvement of non-Hodgkins lymphoma were confirmed by follow-up radiographs and CT and/or a histological biopsy. The detection rate of WB-MRI was high. More bone marrow involvement was detected by biopsy, and more lesions were detected by scintigraphies. In total, 89 lesions were detected by WB-MRI, whereas 15 were found by biopsy, 5 by ⁶⁷Ga scintigraphy, and 14 by bone scintigraphy. WB-MRI could also detect more extramedullary lesions than ⁶⁷Ga scintigraphy; i.e., 72 lesions were detected by WB-MRI, whereas 54 were discovered by ⁶⁷Ga scintigraphy. WB-MRI is useful for evaluating the involvement of bone marrow and extramedullary lesions throughout the skeleton in patients with non-Hodgkins lymphoma.     

Detectability of residual invasive bladder cancer in delayed <Superscript>18</Superscript>F-FDG PET imaging with oral hydration using 500 mL of water and voiding-refilling

Objective

2-Fluorine-18-fluoro-2-deoxy-d-glucose positron emission tomography (¹⁸F-FDG PET) imaging is not considered useful for assessing bladder cancer due to the physiological uptake of ¹⁸F-FDG in the bladder. Despite reports of the detection of bladder cancer by washing out ¹⁸F-FDG from the bladder, such methods are invasive and impractical in the routine practice. The purpose of this study was to evaluate prospectively the utility of oral hydration with 500 mL of water and voiding-refilling, a minimally invasive method that we introduced to enable detection of residual invasive bladder cancer on delayed ¹⁸F-FDG PET imaging.

Methods

From January 2015 to December 2017, 267 consecutive patients with bladder cancer underwent ¹⁸F-FDG PET/computed tomography scans. Among these patients, 25 (19 men and 6 women; mean age, 72.0?±?11.3 years) were newly diagnosed as having muscle-invasive bladder cancer by transurethral resection of bladder tumor and T3b or T4 by magnetic resonance imaging (MRI). All patients were orally hydrated with only 500 mL of water and were then instructed to void frequently for 60 min before early ¹⁸F-FDG PET imaging. After the scans, they were instructed to hold their urine for 60 min. Then, delayed imaging was performed. Two radiologists evaluated the early and delayed ¹⁸F-FDG PET images to determine whether residual invasive bladder cancer could be detected. The maximum standardized uptake values (SUVmax) of the bladder urine and residual tumor site were also measured on early and delayed images. The maximum diameter of the primary bladder tumor was measured on MRI.

Results

The sensitivity for detecting residual invasive bladder cancer on early and delayed imaging were 24.0 and 92.0%, respectively (P?<?0.001). The SUVmax of the bladder urine on the early and delayed imaging were 34.7?±?29.7 and 16.0?±?10.7 (mean?±?SD), respectively. The SUVmax of the residual tumor site on the early and delayed imaging were range 15.65–30.83 and 10.06–45.70, respectively.

Conclusion

Delayed ¹⁸F-FDG PET imaging with oral hydration using only 500 mL of water and voiding-refilling is useful for detecting residual invasive bladder cancer.

     

PET imaging of α<Subscript>7</Subscript> nicotinic acetylcholine receptors: a comparative study of [<Superscript>18</Superscript>F]ASEM and [<Superscript>18</Superscript>F]DBT-10 in nonhuman primates,and further evaluation of [<Superscript>18</Superscript>F]ASEM in humans

Purpose

The α₇ nicotinic acetylcholine receptor (nAChR) is implicated in many neuropsychiatric disorders, making it an important target for positron emission tomography (PET) imaging. The first aim of this work was to compare two α₇ nAChRs PET radioligands, [¹⁸F]ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-([¹⁸F]fluorodibenzo[b,d]thiophene 5,5-dioxide) and [¹⁸F]DBT-10 (7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-([¹⁸F]fluorodibenzo[b,d]thiophene 5,5-dioxide), in nonhuman primates. The second aim was to assess further the quantification and test-retest variability of [¹⁸F]ASEM in humans.

Methods

PET scans with high specific activity [¹⁸F]ASEM or [¹⁸F]DBT-10 were acquired in three rhesus monkeys (one male, two female), and the kinetic properties of these radiotracers were compared. Additional [¹⁸F]ASEM PET scans with blocking doses of nicotine, varenicline, and cold ASEM were acquired separately in two animals. Next, six human subjects (five male, one female) were imaged with [¹⁸F]ASEM PET for 180 min, and arterial sampling was used to measure the parent input function. Different modeling approaches were compared to identify the optimal analysis method and scan duration for quantification of [¹⁸F]ASEM distribution volume (V _T). In addition, retest scans were acquired in four subjects (three male, one female), and the test-retest variability of V _T was assessed.

Results

In the rhesus monkey brain [¹⁸F]ASEM and [¹⁸F]DBT-10 exhibited highly similar kinetic profiles. Dose-dependent blockade of [¹⁸F]ASEM binding was observed, while administration of either nicotine or varenicline did not change [¹⁸F]ASEM V _T. [¹⁸F]ASEM was selected for further validation because it has been used in humans. Accurate quantification of [¹⁸F]ASEM V _T in humans was achieved using multilinear analysis with at least 90 min of data acquisition, resulting in V _T values ranging from 19.6?±?2.5 mL/cm³ in cerebellum to 25.9?±?2.9 mL/cm³ in thalamus. Test-retest variability of V _T was 11.7?±?9.8%.

Conclusions

These results confirm [¹⁸F]ASEM as a suitable radiotracer for the imaging and quantification of α₇ nAChRs in humans.

     

[<Superscript>18</Superscript>F]FPRGD<Subscript>2</Subscript> PET/CT imaging of integrin α<Subscript>v</Subscript>β<Subscript>3</Subscript> levels in patients with locally advanced rectal carcinoma

Purpose

Our primary objective was to determine if [¹⁸F]FPRGD₂ PET/CT performed at baseline and/or after chemoradiotherapy (CRT) could predict tumour regression grade (TRG) in locally advanced rectal cancer (LARC). Secondary objectives were to compare baseline [¹⁸F]FPRGD₂ and [¹⁸F]FDG uptake, to evaluate the correlation between posttreatment [¹⁸F]FPRGD₂ uptake and tumour microvessel density (MVD) and to determine if [¹⁸F]FPRGD₂ and FDG PET/CT could predict disease-free survival.

Methods

Baseline [¹⁸F]FPRGD₂ and FDG PET/CT were performed in 32 consecutive patients (23 men, 9 women; mean age 63?±?8 years) with LARC before starting any therapy. A posttreatment [¹⁸F]FPRGD₂ PET/CT scan was performed in 24 patients after the end of CRT (median interval 7 weeks, range 3 – 15 weeks) and before surgery (median interval 4 days, range 1 – 15 days).

Results

All LARC showed uptake of both [¹⁸F]FPRGD₂ (SUV_max 5.4?±?1.5, range 2.7 – 9) and FDG (SUV_max 16.5?±?8, range 7.1 – 36.5). There was a moderate positive correlation between [¹⁸F]FPRGD₂ and FDG SUV_max (Pearson’s r?=?0.49, p?=?0.0026). There was a moderate negative correlation between baseline [¹⁸F]FPRGD₂ SUV_max and the TRG (Spearman’s r?=??0.37, p?=?0.037), and a [¹⁸F]FPRGD₂ SUV_max of >5.6 identified all patients with a complete response (TRG 0; AUC 0.84, 95 % CI 0.68 - 1, p?=?0.029). In the 24 patients who underwent a posttreatment [¹⁸F]FPRGD₂ PET/CT scan the response index, calculated as [(SUV_max1 ? SUV_max2)/SUV_max1] × 100 %, was not associated with TRG. Post-treatment [¹⁸F]FPRGD₂ uptake was not correlated with tumour MVD. Neither [¹⁸F]FPRGD₂ nor FDG uptake predicted disease-free survival.

Conclusion

Baseline [¹⁸F]FPRGD₂ uptake was correlated with the pathological response in patients with LARC treated with CRT. However, the specificity was too low to consider its clinical routine use.