brain MRI image brain MRI image

Imaging Phenotypes May Provide
a Novel Biomarker Approach

Phenotypic precision medicine may facilitate decision making based on observable characteristics that are produced through the interaction of a genotype and environment.1-6 Phenotypes can be assessed through noninvasive diagnostics, such as PSMA PET/computed tomography (CT) imaging.3,7-12

In contrast, the analysis of genotypes requires the collection of biologic samples, which can be complicated to do in advanced prostate cancer.13-15

Limitations of prostate cancer biopsies include…

Patient image

Morbidity
associated with
biopsy of primary
and metastatic
lesions15-18

Tumor image

Bone biopsies
are technically
challenging to
obtain15,19-22

Cellular image

Not all lesions
are amenable
to biopsy13,15,19,20,23

Patient image

Biopsies of a single tumour may not capture intra- and intertumoural heterogeneity13,15,19,24,25

While genotypes require biologic samples for genetic sequencing, imaging phenotypes can be characterized by noninvasive diagnostics: conventional imaging (CT or bone scan) or next-generation imaging (PET/CT).3,7-12

PET imaging leverages radiotracers to visualize cancer tissue at a high sensitivity and specificity.26-31

Commonly used radiotracers include…

Radiotracer (Date of EMA or FDA Approval,
if Applicable) 		Physiologic Target Characteristics
18F-FDG
(EMA: 2012;
FDA: 2005)32,33
F-FDG
Glucose
metabolism32,33
  • Widely available34
  • Meaningful prognostic indicator in APC35
  • Prostate cancer has low glucose metabolism, resulting in low sensitivity34
11C-choline
(FDA: 2012)36
C-choline
Cell
membrane
synthesis36
  • Higher diagnostic sensitivity than FDG-PET/CT37,a
  • Variable sensitivity and specificity for biochemical recurrence, especially at low PSA levels27
  • Short half-life of 20.4 minutes requires an on-site cyclotron27
18F-choline38-49
F-choline
Cell
membrane
synthesis38
  • High diagnostic performance for accurate staging and restaging in patients with prostate cancer50,b
  • Long half-life of 109.8 minutes does not require an on-site cyclotron38,51
  • Higher urinary excretion than 11C-choline, which necessitates continuous bladder irrigation to eliminate bladder radioactivity52
  • Approved in 12 countries in Europe38-49
18F-fluciclovine
(EMA: 2017;
FDA: 2016)53,54
F-fluciclovine
Amino acid transport53,54
  • Useful for restaging, particularly for patients with higher PSA values55
  • Lesion detection rate superior to choline56,c
  • Potential variability in sensitivity and specificity related to location of metastases27
PSMA-based radiotracers
PSMA-based radiotracers
Targets PSMA
  • High specificity and sensitivity, even at low PSA levels12,27,29,57,d-f
  • May provide better biochemical recurrence detection than 18F-fuciclovine12,d
  • 68Ga-PSMA-11 was approved in the USA in December 2020 as a radioactive diagnostic PET imaging agent in men with prostate cancer with suspected metastasis who are potentially curable by surgery or radiation therapy, or with suspected recurrence based on elevated serum PSA level58
APC, advanced prostate cancer; CT, computed tomography; EMA, European Medicines Agency; 18F-FDG, 18F-fluorodeoxyglucose; FDA, US Food and Drug Administration; PET, positron emission tomography; PSA, prostate-specific antigen; PSMA, prostate-specific membrane antigen.
aIn a meta-analysis of the diagnostic performance of 11C-choline carried out on 8 selected studies including 276 patients.37
bIn a meta-analysis of the staging/restaging performance of 18F-choline carried out on 16 patient-based and 4 lesion-based studies in 2122 patients and 1039 lesions, respectively.50
cIn a head-to-head comparison performed in 50 patients radically treated for prostate cancer and presenting with rising PSA levels.56
dIn a prospective, single-center, open-label comparative study, 50 adults with biochemical recurrence after radical prostatectomy and PSA levels <2 ng/mL.12
eIn a meta-analysis of the predictive performance of 68Ga-PSMA in 16 studies involving 1309 patients.29
fIn a single-arm prospective trial of 635 patients with biochemically recurrent prostate cancer who underwent 68Ga-PSMA-11 PET.59

PSMA PET imaging is a noninvasive diagnostic approach that may impact treatment decisions in advanced prostate cancer.3-5,7-9

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

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