Personalized medicine represents a major goal in oncology. It has its underpinning in the identification of biomarkers with diagnostic, prognostic, or predictive values. Nowadays, the concept of biomarker no longer necessarily corresponds to biological characteristics measured ex vivo but includes complex physiological characteristics acquired by different technologies. Positron-emission-tomography (PET) imaging is an integral part of this approach by enabling the fine characterization of tumor heterogeneity in vivo in a non-invasive way. It can effectively be assessed by exploring the heterogeneous distribution and uptake of a tracer such as 18F-fluoro-deoxyglucose (FDG) or by using multiple radiopharmaceuticals, each providing different information. These two approaches represent two avenues of development for the research of new biomarkers in oncology. In this article, we review the existing evidence that the measurement of tumor heterogeneity with PET imaging provide essential information in clinical practice for treatment decision-making strategy, to better select patients with poor prognosis for more intensive therapy or those eligible for targeted therapy.

Background In this retrospective study, we investigated the impact of 68Ga‐PSMA‐11 PET‐CT (PSMA PET‐CT) upon the treatment plan and therapeutic response obtained for Prostate Cancer (PCa) patients presenting an occult biochemical recurrence. Methods Forty‐two patients with previously negative or doubtful 18F‐Choline (FCH) were enrolled. PET images were recorded 1 h after injection of tracer. Only a few months after treatment ended, a PSA assay was requested to evaluate the therapeutic efficacy of the treatment based on PSMA results. Results PSMA—positive lesions were detected in 34/42 (80.9%) patients. Detection rates were 85.7% and 89.3% for serum PSA levels lower than 2 ng/mL, and >2 ng/mL, respectively. One hundred seventy‐three lesions were detected: 132/173 in lymph nodes (76.3%), 22/173 as metastatic sites (bone or lung) (12.7%), and 19/173 in the prostate bed (10.9%). As a result of the PSMA PET‐CT, therapeutic management changed in 31/42 patients (73.8%). With a follow‐up of 4.9 ± 2.27 months, 32/42 (76.2%) PSA assays after treatment guided by PSMA PET‐CT were collected. For 37.5% (12/32) of patients, the serum PSA level was lower than 0.2 ng/mL and a PSA decrease of over 50% in 8 (25.0%) other patients were obtained. Conclusion Performing a PSMA PET‐CT when FCH PET‐CT was doubtful or negative allows the recurrence localization in more 80% of patients and this had a major clinical impact, as it resulted in treatment change in more than 70% of patients as well as a significant decrease in PSA levels in more than 60% of them.