Improved Prostate Cancer Detection Using HP 13C MRI - Coming to a treatment center near you?

[cujoe]

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

[MateoBeach]

OK K-9, this calls for a step back to consider the biochemistry.

What they are using to generate a unique signal on an MRI is 1-13C pyruvate. This means a heavier isotope of Carbon, C13 vs normal C12 with one less neutron is placed at the number 1 position of the 4 carbon molecule.. This makes the hydrogens in the vicinity respond to the MRI magnetic depolarization differently (hyper polarized) so it is readily detected on the scan reports.

Lactate and pyruvate are rapidly inter converted into each other via the reversible enzyme Lactate dehydrogenase (LDH). The fate depends on the current state of energy metabolism. Under “normal” aerobic metabolism pyruvate is shuttled into the mitochondria and enters the Krebb’s cycle in the normal direction and is metabolically “burned” to CO2 and H2O and generates abundant usable energy (ATP).

Under anaerobic conditions, or even with adequate Oxygen in the Warburg’ effect of “aerobic” glycolysis, it is fermented instead of fully oxidized. This produces less ATP but generates carbon “building materials” (amino acids, fatty acids, nucleic acid precursors, etc.) required for the rapid building of new cells in replicating cancer.

So I believe they are saying that, in this TRAMP mouse model, they are using the relative ratios of Pyruvate (aerobic precursor, to Lactate (anaerobic product) and Alanine ( amino acid for tissue building) to characterize the ratio of channels or flows for these modes of metabolism. Of course we know it is not all or none. They are all active and vary in degrees of predominance. It is the flow of traffic of small carbon molecules. The flow follows demand and is different in higher grade cancer sub-populations.

Note that this is is the same difference in energy metabolism that makes FDG Glucose PET scans positive in advanced cancer where anaerobic glycolysis has become predominant.

Hope that I have not made too much of a mess of presenting the processes. Any errors are mine. Those who would explore it all deeply are referred to Nick Lane’s “Transformers”. MB, the plodding mule.

[cujoe in reply to MateoBeach]

Desollador de mulas - I was expecting you would chime in on the supporting metabolism in the second (deep dive) paper. Unless Nick Lane himself is reading here, I doubt anyone else could do much "chiming".

As for the similarity to FDG, I guessed as much. It seems the advantage to this scan tech is that is that it is MRI-based (no radiation exposure) and can be used as a companion in initially diagnosing an intact prostate. That would add a layer of diagnostic information that could help distinguish aggressive disease from more indolent forms. Better info should mean better treatment decisions.

My eReader is on its way back to me, so later this week I can finally begin my quest to find the answer to the question we all ask: (Power, Sex, Suicide: Mitochondria and) The Meaning of Life.

Enjoy that sun, Bro'. Ciao - K9 Terror

[NPfisherman in reply to MateoBeach]

Pablo,

A great breakdown of the TCA cycle and explanation of how the scan works in following the differences in cellular metabolism.

Plodding ??? Hardly.... A racing mule, perhaps...

Dangerous Dave

[NPfisherman]

K9 Wonder,

Thanks for posting this information. The Science is Coming!!! In this case, a newer scan which can identify the difference between indolent and aggressive disease, and change the treatment paradigm accordingly...

New medications + New Scans= Precision Medicine + Improved Outcomes

We may yet see PCa hit the chronic disease state that HIV has seen in our lifetimes. Yes, I predicted in 5 years last year... But the disease state evolution is based on more than just the Science... The F factor plays a huge role in getting there...

Funding !!!

Long live the Science... and more Funding, please !!!

DonP