Radiolabeled Somatostatin Analogs for Cancer Imaging.

Somatostatin receptors (SSTR) are expressed by many tumours especially those related to neuro-endocrine origin and molecular functional imaging of SSTR expression using radiolabelled somatostatin analogs have revolutionized imaging of patients with these group of malignancies. Coming a long way from the first radiolabelled somatostatin analog 123I-Tyr-3-octreotide, there has been significant developments in terms of radionuclides used, the ligands and somatostatin derivatives. 111In-Pentetreotide extensively employed for imaging NETs at the beginning has now been replaced by 68Ga-SSA based PET-CT. SSA-PET/CT performs superior to conventional imaging modalities and has evolved in the mainframe for NET imaging. The advantages were multiple: (i) superior spatial resolution of PET versus SPECT, (ii) quantitative capabilities of PET aiding in disease activity and treatment response monitoring with better precision, (iii) shorter scan time and (iv) less patient exposure to radiation. The modality is indicated for staging, detecting the primary in CUP-NETs, restaging, treatment planning (along with FDG: the concept of dual-tracer PET-CT) as well as treatment response evaluation and follow-up of NETs. SSA PET/CT has also been incorporated in the guidelines for imaging of Pheochromocytoma-Paraganglioma, Medullary carcinoma thyroid, Meningioma and Tumor induced osteomalacia. At present, there is rising interest on (a) 18F-labelled SSA, (b) 64Cu-labelled SSA, and (c) somatostatin antagonists. 18F offers excellent imaging properties, 64Cu makes delayed imaging feasible which has implications in dosimetry and SSTR antagonists bind with the SST receptors with high affinity and specificity, providing high contrast images with less background, which can be translated to theranostics effectively. SSTR have been demonstrated in non-neuroendocrine tumours as well in the peer-reviewed literature, with studies demonstrating the potential of SSA PET/CT in Neuroblastoma, Nasopharyngeal carcinoma, carcinoma prostate (neuroendocrine differentiation) and lymphoma. This review will focus on the currently available SSAs and their history, different SPECT/PET agents, SSTR antagonists, comparison between the various imaging tracers, and their utility in both neuroendocrine and non-neuroendocrine tumors.

[64Cu]Copper chloride PET-CT: a comparative evaluation of fasting and non-fasting states in patients of prostate carcinoma.

Altered copper metabolism in cancer has been linked to increased intracellular copper uptake mediated by human copper transporter 1, with [64Cu]Cu2+ as a potential biomarker for cancer theranostics. [64Cu]CuCl2 PET-CT though explored in various malignancies, a lack of standardized protocol exists, particularly regarding fasting status before imaging. This analysis aimed to evaluate the requirement of fasting for [64Cu]CuCl2 PET-CT along with temporal changes in physiological organ uptake in delayed scans. A total of 26 patients of prostate carcinoma who underwent [64Cu]CuCl2 PET-CT imaging were divided into two groups: (1) nonfasting (n = 12) and (2) fasting (n = 14). The nonfasting group received an average dose of 350 MBq, while the fasting group received 300 MBq of [64Cu]CuCl2, and PET-CT images acquired approximately 60-90 min (1 h image) and 3-3.5 h (delayed image) after intravenous injection of the tracer. An experienced nuclear medicine physician evaluated the images for qualitative assessment between the groups. Multiple spherical regions of interest were placed at sites of physiological organ uptake of the tracer and over the diseased lesions to measure the mean SUVmax. No significant difference was observed in the qualitative assessment of the images between the two groups (except for a slight predilection towards more hepatic tracer retention observed in the fasting group), including in the delayed images. The liver demonstrated the highest tracer uptake in all patients, with a mean SUVmax of 21.5 in the fasting group and 19.7 in the nonfasting group, showing no significant difference (P = 0.32). The kidneys, intestines, and salivary glands also showed similar trends of tracer uptake in both groups. The study illustrated that the fasting or nonfasting status did not affect image quality or semiquantitative measurements significantly in physiological organs and diseased lesions in patients with carcinoma prostate.

Incidental Detection of Second Primary Thyroid Malignancy in Patients of Metastatic Castration-Resistant Prostate Carcinoma: Documentation on 68 Ga-PSMA-11 and 64 CuCl 2 PET/CT.

ABSTRACT: Second primary tumors are being increasingly detected owing to and in proportion to the use of advanced imaging modalities including PET/CT. Patients suffering from prostate cancer have been reported to have increased second primary cancers of gastrointestinal tract, urinary bladder, and thyroid. We herein describe incidental detection of thyroid carcinoma, in 2 patients of mCRPC (metastatic castration-resistant prostate carcinoma) undergoing preradioligand therapy workup, on 68 Ga-prostate-specific membrane antigen PET/CT initially, subsequently also observed on multitracer PET/CT ( 64 CuCl 2 and 18 F-FDG). Thus, the potential of PET/CT for early in vivo second primary detection in mCRPC setting is illustrated in the aforementioned 2 patients.

68 Ga-PSMA-11 PET/CT and 64 CuCl 2 PET/CT Help in Identifying Rare Metastatic Site of Penile Shaft in a Patient of Carcinoma Prostate.

ABSTRACT: A 71-year-old man, presenting with complaints of burning sensation and pain during urination, finally diagnosed with prostate carcinoma. Ultrasonography of the abdomen and pelvis revealed prostatomegaly. Serum PSA level was elevated, and TRUS-guided biopsy demonstrated acinar adenocarcinoma (Gleason score: 5 + 4 = 9). 68 Ga-PSMA-11 PET/CT for initial staging showed PSMA-avid enlarged prostate, pelvic lymphadenopathy, and focal PSMA uptake in the left side of the shaft of the penis. The patient also underwent a 64 CuCl 2 PET/CT, which demonstrated similar findings of enlarged prostate and adenopathy with focally increased tracer uptake in the shaft of the penis coinciding with the lesion observed on 68 Ga-PSMA-11 PET/CT, thereby detecting a rare metastatic site from carcinoma prostate.

Exploratory analysis of 64 CuCl 2 PET-CT imaging in carcinoma prostate and its comparison with 68 Ga-PSMA-11 and 18 F-FDG PET-CT.

AIM: Exploratory analysis of 64 CuCl 2 PET-CT imaging in patients of carcinoma prostate and its head-to-head comparison with 68 Ga-PSMA-11 and 18 F-FDG PET-CT. METHODS: In this prospective study, 50 patients of biopsy-proven carcinoma prostate belonging to the entire spectrum of disease were evaluated, out of which 21 patients were for initial staging and 29 were for restaging/response evaluation. Both 64 CuCl 2 (early and delayed) and 68 Ga-PSMA-11 PET-CT were undertaken in all patients and 18 F-FDG PET-CT was done in patients whenever possible. All scans were done within a period of 2 weeks, without any interim therapeutic intervention. 64 CuCl 2 PET-CT was acquired at 1 and 3 h. We evaluated the physiological uptake of 64 CuCl 2 , correlated the uptake in primary with disease parameters like Gleason score and serum PSA levels, and compared the detection rates for primary and metastatic disease with 68 Ga-PSMA-11 and 18 F-FDG PET-CT. RESULTS: The detection rates of primary disease were same for both 64 CuCl 2 and 68 Ga-PSMA-11 PET-CT and both agents performed similarly in detecting extra-prostatic disease. There was no statistically significant correlation observed between the uptake of 64 CuCl 2 in the primary lesion with disease parameters. With regard to the evaluation of metastatic disease, the detection rate of 64 CuCl 2 PET-CT was 86% for lymph nodes, 77.3% for skeletal metastases and 80.6% for soft tissue metastases while 68 Ga-PSMA-11 PET-CT performed better with detection rates were 98%, 99% and 85.4%, respectively. In 17 patients where 18 F-FDG PET-CT was available, 64 CuCl 2 PET-CT detected more metastatic disease than 18 F-FDG PET-CT. CONCLUSION: 64 CuCl 2 PET-CT did not show any additional advantage over 68 Ga-PSMA-11 PET-CT in evaluation of local disease or for the assessment of metastatic disease. When compared to 68 Ga-PSMA-11 PET-CT, the absence of urinary bladder and ureteric activity allows better contrast for evaluating local disease, but it does not translate into increased disease detection.

Angiogenesis Imaging of Adrenocortical Carcinoma with Ga-68-NODAGA-RGD Positron Emission Tomography: Opening New Horizons in Multimodality Imaging from Theranostic Perspective.

A 53-year-old female, with a known case of adrenocortical carcinoma (ACC), underwent F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for initial staging, which revealed FDG avid large left suprarenal mass contiguous with hypermetabolic tumor thrombus in the inferior vena cava (IVC) through the left renal vein. Thereafter, she underwent angiogenesis imaging using Ga-68-NODAGA-RGD PET/CT, which showed similar avid tracer uptake in both primary and IVC thrombus. Demonstration of RGD avidity in ACC in this case opens a new horizon for targeted radionuclide therapy (e.g., Lu-177 RGD) in selected patients, who may have limited therapeutic options.