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18F-MK-9470 PET imaging of the type 1 cannabinoid receptor in prostate carcinoma: a pilot study.

Emonds KM, Koole M, Casteels C, Van den Bergh L, Bormans GM, Claus F, De Wever L, Lerut E, Van Poppel H, Joniau S, Dumez H, Haustermans K, Mortelmans L, Goffin K, Van Laere K, Deroose CM, Mottaghy FM - EJNMMI Res (2013)

Bottom Line: For three patients with proven advanced metastatic disease, two static PET/CTs were performed 1 and 3 h post-injection. 18F-MK-9470 uptake was evaluated in bone lesions of metastatic PCa by comparing SUVmean values of metastases with these of the contralateral bone tissue. 18F-MK-9470 uptake was significantly higher in benign and malignant prostate tissue compared to muscle, but it did not differ between both prostate tissue compartments.Metastases in the axial skeleton could not be detected while some metastases in the appendicular skeleton showed higher 18F-MK-9470 uptake as compared to the uptake in contralateral normal bone. 18F-MK-9470 PET could not detect local PCa or bone metastases in the axial skeleton but was able to visualize metastases in the appendicular skeleton.Based on these pilot observations, it seems unlikely that CB1R PET will play a significant role in the evaluation of PCa.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Nuclear Medicine, University Hospitals Leuven, Leuven 3000, Belgium. fmottaghy@ukaachen.de.

ABSTRACT

Background: Preclinical and histological data show overexpression of the type 1 cannabinoid receptor (CB1R) in prostate carcinoma (PCa). In a prospective study, the feasibility of 18F-MK-9470 positron emission tomography (PET) imaging in patients with primary and metastatic PCa was evaluated.

Methods: Eight patients were included and underwent 18F-MK-9470 PET/CT imaging. For five patients with primary PCa, dynamic PET/CT imaging was performed over three acquisition intervals (0 to 30, 60 to 90 and 120 to 150 min post-injection). In malignant and benign prostate tissue regions, time activity curves of the mean standardized uptake value (SUVmean) were determined as well as the corresponding area under the curve to compare 18F-MK-9470 uptake over time. Muscle uptake of 18F-MK-9470 was used as reference for non-specific binding. Magnetic resonance imaging (MRI) was used as anatomical reference and for delineating intraprostatic tumours. Histological and immunohistochemical (IHC) examination was performed on the whole-mount histopathology sections of four patients who underwent radical prostatectomy to assess the MRI-based tumour versus benign tissue classification. For three patients with proven advanced metastatic disease, two static PET/CTs were performed 1 and 3 h post-injection. 18F-MK-9470 uptake was evaluated in bone lesions of metastatic PCa by comparing SUVmean values of metastases with these of the contralateral bone tissue.

Results: 18F-MK-9470 uptake was significantly higher in benign and malignant prostate tissue compared to muscle, but it did not differ between both prostate tissue compartments. IHC findings of corresponding prostatic histopathological sections indicated weak CB1R expression in locally confined PCa, which was not visualized with 18F-MK-9470 PET. Metastases in the axial skeleton could not be detected while some metastases in the appendicular skeleton showed higher 18F-MK-9470 uptake as compared to the uptake in contralateral normal bone.

Conclusions: 18F-MK-9470 PET could not detect local PCa or bone metastases in the axial skeleton but was able to visualize metastases in the appendicular skeleton. Based on these pilot observations, it seems unlikely that CB1R PET will play a significant role in the evaluation of PCa.

No MeSH data available.


Related in: MedlinePlus

Overview of CB1R expression in prostate tissue. Prostate tissue sections were obtained after RP of four patients (original magnification ×100). In non-tumoural prostatic epithelium in general, no expression was seen (A), although some randomly distributed areas of weak positivity were noted (B). In PCa, the overall expression pattern was a mixture of negative (C) and weak positive (D) areas. Some foci of moderate positivity were randomly dispersed (E). CB1R expression in the seminal vesicles was used as an internal positive control (F).
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Figure 5: Overview of CB1R expression in prostate tissue. Prostate tissue sections were obtained after RP of four patients (original magnification ×100). In non-tumoural prostatic epithelium in general, no expression was seen (A), although some randomly distributed areas of weak positivity were noted (B). In PCa, the overall expression pattern was a mixture of negative (C) and weak positive (D) areas. Some foci of moderate positivity were randomly dispersed (E). CB1R expression in the seminal vesicles was used as an internal positive control (F).

Mentions: In the specimen of the surgically removed prostate, the detection of CB1R expression as measured with IHC was comparable in the tissue sections of all four patients. The majority of the non-tumoural prostatic epithelium showed no CB1R expression (Figure 5A). Heterogeneously distributed throughout the tissue, some foci of weak expression were seen (Figure 5B), and very rarely, a few moderately positive glands were present. Strong CB1R expression was absent in the non-tumoural prostate parenchyma. CB1R was expressed in the cytoplasm of cells but not in nuclei and on the cell membrane.


18F-MK-9470 PET imaging of the type 1 cannabinoid receptor in prostate carcinoma: a pilot study.

Emonds KM, Koole M, Casteels C, Van den Bergh L, Bormans GM, Claus F, De Wever L, Lerut E, Van Poppel H, Joniau S, Dumez H, Haustermans K, Mortelmans L, Goffin K, Van Laere K, Deroose CM, Mottaghy FM - EJNMMI Res (2013)

Overview of CB1R expression in prostate tissue. Prostate tissue sections were obtained after RP of four patients (original magnification ×100). In non-tumoural prostatic epithelium in general, no expression was seen (A), although some randomly distributed areas of weak positivity were noted (B). In PCa, the overall expression pattern was a mixture of negative (C) and weak positive (D) areas. Some foci of moderate positivity were randomly dispersed (E). CB1R expression in the seminal vesicles was used as an internal positive control (F).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750838&req=5

Figure 5: Overview of CB1R expression in prostate tissue. Prostate tissue sections were obtained after RP of four patients (original magnification ×100). In non-tumoural prostatic epithelium in general, no expression was seen (A), although some randomly distributed areas of weak positivity were noted (B). In PCa, the overall expression pattern was a mixture of negative (C) and weak positive (D) areas. Some foci of moderate positivity were randomly dispersed (E). CB1R expression in the seminal vesicles was used as an internal positive control (F).
Mentions: In the specimen of the surgically removed prostate, the detection of CB1R expression as measured with IHC was comparable in the tissue sections of all four patients. The majority of the non-tumoural prostatic epithelium showed no CB1R expression (Figure 5A). Heterogeneously distributed throughout the tissue, some foci of weak expression were seen (Figure 5B), and very rarely, a few moderately positive glands were present. Strong CB1R expression was absent in the non-tumoural prostate parenchyma. CB1R was expressed in the cytoplasm of cells but not in nuclei and on the cell membrane.

Bottom Line: For three patients with proven advanced metastatic disease, two static PET/CTs were performed 1 and 3 h post-injection. 18F-MK-9470 uptake was evaluated in bone lesions of metastatic PCa by comparing SUVmean values of metastases with these of the contralateral bone tissue. 18F-MK-9470 uptake was significantly higher in benign and malignant prostate tissue compared to muscle, but it did not differ between both prostate tissue compartments.Metastases in the axial skeleton could not be detected while some metastases in the appendicular skeleton showed higher 18F-MK-9470 uptake as compared to the uptake in contralateral normal bone. 18F-MK-9470 PET could not detect local PCa or bone metastases in the axial skeleton but was able to visualize metastases in the appendicular skeleton.Based on these pilot observations, it seems unlikely that CB1R PET will play a significant role in the evaluation of PCa.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Nuclear Medicine, University Hospitals Leuven, Leuven 3000, Belgium. fmottaghy@ukaachen.de.

ABSTRACT

Background: Preclinical and histological data show overexpression of the type 1 cannabinoid receptor (CB1R) in prostate carcinoma (PCa). In a prospective study, the feasibility of 18F-MK-9470 positron emission tomography (PET) imaging in patients with primary and metastatic PCa was evaluated.

Methods: Eight patients were included and underwent 18F-MK-9470 PET/CT imaging. For five patients with primary PCa, dynamic PET/CT imaging was performed over three acquisition intervals (0 to 30, 60 to 90 and 120 to 150 min post-injection). In malignant and benign prostate tissue regions, time activity curves of the mean standardized uptake value (SUVmean) were determined as well as the corresponding area under the curve to compare 18F-MK-9470 uptake over time. Muscle uptake of 18F-MK-9470 was used as reference for non-specific binding. Magnetic resonance imaging (MRI) was used as anatomical reference and for delineating intraprostatic tumours. Histological and immunohistochemical (IHC) examination was performed on the whole-mount histopathology sections of four patients who underwent radical prostatectomy to assess the MRI-based tumour versus benign tissue classification. For three patients with proven advanced metastatic disease, two static PET/CTs were performed 1 and 3 h post-injection. 18F-MK-9470 uptake was evaluated in bone lesions of metastatic PCa by comparing SUVmean values of metastases with these of the contralateral bone tissue.

Results: 18F-MK-9470 uptake was significantly higher in benign and malignant prostate tissue compared to muscle, but it did not differ between both prostate tissue compartments. IHC findings of corresponding prostatic histopathological sections indicated weak CB1R expression in locally confined PCa, which was not visualized with 18F-MK-9470 PET. Metastases in the axial skeleton could not be detected while some metastases in the appendicular skeleton showed higher 18F-MK-9470 uptake as compared to the uptake in contralateral normal bone.

Conclusions: 18F-MK-9470 PET could not detect local PCa or bone metastases in the axial skeleton but was able to visualize metastases in the appendicular skeleton. Based on these pilot observations, it seems unlikely that CB1R PET will play a significant role in the evaluation of PCa.

No MeSH data available.


Related in: MedlinePlus