Editing Prostate Cancer: Diagnosis and evaluation (section)

====== Prostate cancer PET radiopharmaceutical tracers ======
* '''<span style="color:#ff0000">Not PSMA-specific radiopharmaceutical tracers'''
** Examples include '''<span style="color:#ff0000">18F-fluciclovine (trade name Axumin)</span>''', 18F-fluorodeoxyglucose (FDG), and 11C-choline
*** 18F-fluciclovine FDA approved in 2016
** '''Replaced by PSMA-specific tracers'''
*** '''Lower sensitivity and specificity than PSMA-specific ligands'''
**** In a 2019 prospective study of males who had undergone prostatectomy and had a rising PSA still under 2.0ng/mL, 68Ga-PSMA-PET detected occult metastases 4.54x significantly more frequently than 18F-fluciclovine-PET[https://pubmed.ncbi.nlm.nih.gov/31375469/]
* '''<span style="color:#ff0000">PSMA-specific radiopharmaceuticals tracers</span>'''
** '''PET tracers that bind to Prostate-Specific Membrane Antigen (PSMA)'''
*** '''PSMA'''
**** Also known as glutamate carboxypeptidase II (GCP II)
**** A transmembrane glycoprotein
**** '''Highly overexpressed in >90% of prostate cancers'''
***** Increased expression with
****** Increased pathological Gleason grade
****** Castrate-resistance
** '''<span style="color:#ff0000">PSMA-specific radiopharmaceutical tracers used in prostate cancer (2):</span>'''
***'''<span style="color:#ff0000">Fluorine-18 (18F)-labeled PSMA-specific</span>''' (18F-DCFPyL ('''piflufolastat''' F 18) (trade name '''<span style="color:#ff0000">Pylarify</span>'''), 18F-PSMA-1007)
****'''Most commonly used radiotracer in the US and''' (18F-DCFPyL) '''Canada'''
****18F-DCFPyL adverse reactions: headache, altered taste, fatigue[https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-second-psma-targeted-pet-imaging-drug-men-prostate-cancer]
***'''<span style="color:#ff0000">Gallium-68 (68Ga)-labeled PSMA-specific</span>'''
****'''High specificity and sensitivity'''
*****'''Outperforms standard CT and MRI in detection of nodal and osseous metastases.'''
****As of May 2021, only available locally at two sites in California[https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-second-psma-targeted-pet-imaging-drug-men-prostate-cancer]
****'''Excretion: urinary'''
**'''<span style="color:#ff0000">Uptake of PSMA-specific radiopharmaceuticals</span>[https://pubmed.ncbi.nlm.nih.gov/33661093/]'''
***'''<span style="color:#ff0000">Physiological</span>'''
****'''<span style="color:#ff0000">High uptake: lacrimal and salivary glands, kidneys</span>'''
****'''<span style="color:#ff0000">Moderate uptake: spleen, nasopharynx</span>''' 
**** '''Variable uptake: vocal cords, trachea, bronchi, proximal GI tract'''
**** '''Uptake also seen in central nervous system and peripheral nervous system''' (ganglia and nerve routes)
***** Celiac and stellate ganglia may be false-positives for retroperitoneal and supraclavicular lymphadenopathy
*** '''<span style="color:#ff0000">Benign disease</span>'''
***# '''<span style="color:#ff0000">Infectious and inflammatory processes</span> (e.g., sarcoidosis)'''
***#* Increased blood flow and vascular permeability may partly explain the increased PSMA uptake in inflammatory conditions.
***# '''<span style="color:#ff0000">Benign neoplasms</span>''' (mesenchymal tumors (vascular, neurogenic, connective tissue origin) and epithelial tumors (edenoma and thymoma))
***# '''<span style="color:#ff0000">Bone remodelling</span>''' (healing fractures, degenerative or arthritic processes (e.g., osteophytes), Paget's disease)
***# '''<span style="color:#ff0000">Amyloidosis</span>'''
*** '''<span style="color:#ff0000">Malignancy</span>'''
**** '''<span style="color:#ff0000">Prostate cancer</span>'''
**** '''<span style="color:#ff0000">Non-prostate malignancies</span>'''
***** '''<span style="color:#ff0000">Renal cell carcinoma</span>,''' leiomyosarcoma, thyroid cancer, nasopharyngeal cancer, GI tract cancer, breast cancer, neuroendocrine cancer
** '''<span style="color:#ff0000">Clearance of PET tracers used in prostate cancer</span>[https://pubmed.ncbi.nlm.nih.gov/33661093/]'''
*** '''<span style="color:#ff0000">Most are cleared via the urinary tract</span>, with high accumulation in the urinary tract and bladder and moderate uptake in the liver'''
**** '''Exception: 18F-PSMA-1007, 18F-fluciclovine, and 11-choline</span> are cleared primarily by the hepatobiliary tract, with higher uptake in the liver, and little accumulation in the ureters and bladder'''
***** '''<span style="color:#ff0000">Clinical implication: since 18F-PSMA-1007, 18F-fluciclovine, and 11-choline have minimal excretion from the urinary tract, use of these tracers may aid in identifying disease sites adjacent to the bladder and ureters, such as local tumor recurrence after prostatectomy.</span>'''
** '''<span style="color:#ff0000">Causes of false-negative PSMA-targeted PET</span>'''
**# '''<span style="color:#ff0000">Small tumor volume</span>'''
**#* May be seen in early-stage biochemical recurrence when the serum PSA <0.5 ng/ml
**# '''<span style="color:#ff0000">Neuroendocrine differentiation of prostate cancer</span>''' with downregulation of PSMA expression
**#* Neuroendocrine differentiation occurs in 5–10% of prostate cancers overall and approximately 30% of men with advanced disease
**# '''<span style="color:#ff0000">Androgen receptor inhibition</span>'''
**#* '''Short-term ADT likely increases PSMA-targeted PET positivity, whereas prolonged, continuous ADT is associated with a higher likelihood of a negative PSMA-targeted PET'''