As the complexity of the genetic/epigenetic nature of cancer has become evident, significant research focus has once again returned to cancer metabolism. This new MRI technology (HP 13C MRI) promises to capture and identify specific metabolic characteristics of PCa that have not been possible with exiting scan technologies.
As an example, UCSF now has a program in place to test the effectiveness of HP 13C MRI to identify PCa tumors via metabolic distinctions and help categorize their aggressiveness. The Press Release from September of this year says in part:
"HP 13C MRI provides a quick five-minute, non-radioactive, metabolic imaging add-on exam to standard-of-care MRI that, in conjunction with guided biopsies, has great potential to improve the care of prostate cancer patients,” says Robert Bok, MD, PhD, professor in the Department of Radiology & Biomedical Imaging and the HMTRC. “The rapid assessment of the presence and aggressiveness of a patient’s cancer has the potential to provide patients with an individualized approach to cancer treatment,” adds Michael Ohliger, MD, PhD, an associate professor in Radiology & Biomedical Imaging and HMTRC member.
The full PR is here:
UCSF Investigators Improve MR-guided TRUS Fusion Biopsy for Prostate Cancer Detection Using HP 13C MRI - UCSF Department of Radiology & Biomedical Imaging - Research News, September 30, 2022
radiology.ucsf.edu/blog/ucs...
And for those who want to do a REAL deep dive into Hyperpolarised 13C-MRI, here is a very technical paper from a lot of smart people in the UK that will tell you all you want/need to know:
Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer - Nature Communications - Article, Published: 24 January 2022
nature.com/articles/s41467-...
Abstract
Hyperpolarised magnetic resonance imaging (HP 13C-MRI) is an emerging clinical technique to detect [1-13C]lactate production in prostate cancer (PCa) following intravenous injection of hyperpolarised [1-13C]pyruvate. Here we differentiate clinically significant PCa from indolent disease in a low/intermediate-risk population by correlating [1-13C]lactate labelling on MRI with the percentage of Gleason pattern 4 (%GP4) disease. Using immunohistochemistry and spatial transcriptomics, we show that HP 13C-MRI predominantly measures metabolism in the epithelial compartment of the tumour, rather than the stroma. MRI-derived tumour [1-13C]lactate labelling correlated with epithelial mRNA expression of the enzyme lactate dehydrogenase (LDHA and LDHB combined), and the ratio of lactate transporter expression between the epithelial and stromal compartments (epithelium-to-stroma MCT4). We observe similar changes in MCT4, LDHA, and LDHB between tumours with primary Gleason patterns 3 and 4 in an independent TCGA cohort. Therefore, HP 13C-MRI can metabolically phenotype clinically significant disease based on underlying metabolic differences in the epithelial and stromal tumour compartments.
Key findings from the report:
HP 13C-MRI detects occult prostate lesions and enables non-invasive metabolic phenotyping of multifocal disease
HP [1-13C]lactate labelling correlates with the percentage of Gleason pattern 4 disease and tumour cellularity but not vascular permeability
Single-gland analysis of MCT and LDH expression reveals metabolic progression towards increased glycolysis in Gleason pattern 5 gland
TCGA data from a large prostatectomy cohort corroborates the observed changes in MCT4, LDHA, and LDHB expression
And from the Discussion Section, the following:
In conclusion, this study demonstrates differential [1-13C]lactate labelling in intermediate-risk PCa with varying percentage pattern 4 components and confirms the ability of HP 13C-MRI to provide additional information to grade-dependent disease differentiation used as part of standard of care. We provide evidence that increasing [1-13C]lactate labelling in more aggressive disease is a reflection of tumour epithelial cell metabolism, as opposed to stromal metabolism, as demonstrated by an increase in the combined tumour epithelial LDH expression and epithelium-to-stroma MCT4 ratio. We have also demonstrated a possible reciprocal relationship between tumour glycolysis and oxidative metabolism, as evidenced by the LDHA/PDHA1 expression ratio, and high nuclear HIF-1α expression in malignant glands of the most aggressive histological pattern, which may explain the increase in LDHA expression. These findings have demonstrated the ability of HP 13C-MRI to non-invasively differentiate indolent from aggressive prostate tumours based on their characteristic metabolic features. If validated in larger patient cohorts, these findings have translational potential to address important unmet clinical questions for patients with PCa using a novel imaging modality. (emphasis added)
Another example of Don Pescado's "Science is coming". (Patience, Grasshopper.)
Ciao - K9
