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Sella turcica and petrous bone metastasis from differentiated thyroid carcinoma are rare clinical entities, with only a few limited cases reported to date. Two cases, one of sella turcica metastasis and the other of petrous bone metastasis from carcinoma of the thyroid gland, are presented. The cases diagnosed to have arisen from poorly differentiated thyroid carcinoma and follicular carcinoma of thyroid, respectively, subsequently underwent total thyroidectomy, radioiodine (RAI) scans and RAI therapies with iodine-131, external radiotherapy, and levothyroxine suppression with follow-up. Their clinical symptoms gradually subsided, with reduction in serum thyroglobulin, and finally resulted in disease stabilization. With the multimodality therapeutic approach, both patients are alive to date, with 48- and 60-month survival post diagnosis, respectively.

A 50-year-old female patient of heavily pre-treated (chemotherapy and multiple treatment-resistant) and progressive intermediate-grade metastatic neuroendocrine neoplasm is presented, wherein the lesions showed mixed response following topotecan treatment and multiple hepatic metastasis showed increase in the SSTR expression and decrease in FDG concentration on dual-tracer PET/CT (68Ga-DOTATATE and 18F-FDG PET/CT). Such observation allowed 177Lu-DOTATATE PRRT to be considered for an advanced, symptomatic, and multiple treatment-resistant patient with limited palliative treatment options left.

Pulmonary metastases in thyroid carcinoma demonstrates varying imaging characteristics and disease biology and the outcome. The valuable complimentary role of high-resolution CT (HRCT) in conjunction with functional imaging such as radioiodine scan has been discussed and illustrated in this review along with the varied clinical and imaging presentations of lung metastases from differentiated thyroid cancer (DTC). A multi-modality patient-specific diagnostic approach and awareness about the atypical presentations helps in early identification as well as effective management of these patients, and especially in certain situations that could need multi-disciplinary management. While HRCT of the lungs as an added tool provides detailed visualization of the lung parenchyma, in the era of hybrid imaging, the routine adoption of SPECT-CT in patients with pulmonary metastases (in diagnostic or post-treatment settings) could provide equivalent or even incremental information from further management viewpoint.

Most of the established guidelines mention and recommend the use of FDG-PET/CT (fluorodeoxyglucose positron emission tomography/computed tomography) in carcinoma of unknown primary (CUP) especially in head–neck squamous cell carcinoma; as described in this article, this forms a powerful one-stop shop in diagnosing and staging modality and has multiple applications in difficult situations of CUPs. Although not used as a screening modality, FDG-PET/CT is recommended as the primary imaging modality in the evaluation of primary, staging, and response evaluation for CUP with histology known to demonstrate FDG avidity, especially patients presenting with lymph nodal disease. It should be remembered that many histological types do not concentrate on FDG and FDG also shows false-positive results in many other conditions like infection-inflammation; however, at the same time, it delivers high negative predictive values, an important consideration when employing FDG-PET/CT in the CUP scenario. SSTR-based PET/CT plays a pivotal role in primary diagnosis, staging, therapy planning, and response assessment in CUPs with neuroendocrine tumor or neuroendocrine neoplasm histology. The last two decades has witnessed great advancement in PET instrumentation and radiopharmaceuticals: particularly techniques like PET/magnetic resonance imaging and radiopharmaceuticals like FAPI (fibroblast-activation protein inhibitor)-based PET tracers. Hence, the role of PET/CT is expected to expand its reach in the coming years in line with accruing literature evidence, thereby upgrading its role and reliability in oncological practice strategies.

We in this article have presented a review of the guideline recommendations on theranostic positron emission tomography-computed tomography (PET-CT) imaging which will be helpful to assist practitioners in providing appropriate patient care. Multiple guidelines by different societies and medical associations provide standards for diagnosis, imaging, and treatment of cancer patients. They have generated a number of recommendations related to 68Ga-DOTATATE and 68Ga-PSMA-11 PET-CT, which are the classical examples of theranostic PET-CT imaging in current practice.

Hurthle cell thyroid carcinoma (HCTC) demonstrates inferior prognosis compared with other types of differentiated thyroid cancer (DTC), along with radioiodine refractoriness and relatively poor 131I concentrating ability. We herein report a case of a middle-aged lady presenting with neck swelling for years, who on pre-surgery work-up was diagnosed to harbor metastatic nodal and lung lesions. Post-thyroidectomy and neck dissection, she was diagnosed with HCTC. Post-surgery, none of the lesions concentrated radioactive-iodine (RAI) sufficiently but showed FDG avid lesions as mediastinal nodes, lung nodules, solitary lytic sternal lesions, and unusual bilateral paraaortic abdominal nodes. She was put on tyrosine kinase inhibitor (sorafenib) and showed disease stabilization for the initial 3 years, but multiple toxicity symptoms while on sorafenib therapy that needed multiple dose adjustments. Over the period of the subsequent year, she developed significant disease progression with liver involvement. She was shifted to lenvatinib, which she tolerated well. The functional imaging profile with unusual metastatic sites, the aggressive clinical presentation and disease course of RAI refractory HCTC over 4 years on tyrosine kinase inhibitor therapy, and the role of molecular FDG-PET/CT imaging in disease monitoring and clinical management of such case is presented.

We herein illustrate a case of benign tenosynovial giant cell tumor, which was incidentally detected as FDG-avid lesion on PET/CT in a patient with radioiodine refractory thyroid cancer, with predominantly non-iodine concentrating disease. The lesion was followed up clinically and with local MRI annually for subsequent 3 years. The utility of hybrid PET-CT imaging, the non-iodine concentration of the tumor along with clinical knowledge, and findings on other imaging and pathological modalities in answering and diagnosing incidental benign musculoskeletal tumors in a patient with known thyroid malignancy are presented here.

A rare and fatal life-threatening case of necrotizing fasciitis (initially presenting with skin-deep superficial lesions and clinical suspicion of paraneoplastic syndrome) is described, who was finally diagnosed with the help of fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) as more extensive infectious process. A 36-year-old male presented with bilaterally symmetrical cutaneous lesions involving lower limbs that rapidly progressed to ulcerative lesions and pancytopenia. In view of suspicion of paraneoplastic manifestation, the patient underwent 18F-FDG-PET/CT to rule out any underlying malignancy. The FDG-PET/CT findings confirmed hypermetabolism circumferentially along the fasciae of bilateral lower extremities while sparing muscles and subcutaneous fat from below the knee till toe with diffused hypermetabolic marrow, and no evidence of focal disease suggesting malignancy. Biopsy turned out to be superficial necrolytic fasciitis. The patient's condition deteriorated and, 20 days following the scan, the patient succumbed secondary to severe pancytopenia and hypotension. The case raises the importance of high degree of suspicion and prompt diagnosis of this condition, where FDG-PET/CT imaging can play a valuable complimentary role. Such awareness could be lifesaving due to early optimal treatment in the disease course.

Determining the choice and the goal is key element for decision-making of a systemic radionuclide therapy. They should be clearly defined in deciding and individualizing the dose and regimen. For iodine-131 metaiodobenzylguanidine (131I-mIBG) therapy, the important considerations during dose fractionation include disease burden, tumor biology, functional symptoms, and associated comorbidities, all of which are important determinants for the intent and course of treatment. Herein, we present the case of a 67-year-old elderly female with highly functional metastatic recurrent extra-adrenal pheochromocytoma (presenting 42 years after the primary surgery and 32 years following excision of pararenal recurrence) with multiple comorbidities including single kidney and borderline renal compromise, treated successfully with a relatively lower dose of 131I-mIBG (cumulative dose of 22.2 GBq in four cycles with a mean dose of 5.7 GBq per therapy cycle). The excellent tumor burden reduction, hormonal tumor marker response, and most importantly asymptomatic status could be achieved with the administered dose. On follow-up, none of the pretherapeutic parameters (including renal function) showed any further derangement compared with the baseline during next 24 months following the treatment. All cycles were well tolerated with only reversible hematological toxicity that normalized without any active intervention. The report is intended to provide some guidance for future therapeutic regimens.

A patient of differentiated follicular thyroid carcinoma with unusual sites of metastases is illustrated with 131I and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging findings. The described case harbored extremely rare metastasis to the urinary bladder with multi-organ metastatic disease (including unusual sites of right bronchus and hepatic metastases). There was inter-lesional heterogeneity among the metastatic lesions with regard to the 131I and FDG uptake in the aforementioned lesions. The detection of such heterogeneity has important implications for patient management in metastatic differentiated thyroid carcinoma.

The correlates of dual tracer positron emission tomography and computed tomography (PET-CT) (18F-fluorodeoxyglucose [18F-FDG] and 68Ga-DOTATATE) in patients of Grade 3 neuroendocrine neoplasms (NENs) are presented. The first, a patient of gall bladder NEN, operated, with histopathology suggestive of high-grade well-differentiated neuroendocrine tumors with MiB-1 labeling index of 35%, showed uptake with both 18F-FDG and 68Ga-DOTATATE, including an uptake equivalent to Krenning score of 3–4 on 68Ga-DOTATATE PET-CT; in the second, a patient of esophageal NEN, Grade 3 with poor differentiation features, with MiB-1 labeling index of 70%, thereby qualifying for Grade 3 neuroendocrine carcinoma, the FDG uptake was high with minimal uptake on 68Ga-DOTATATE PET-CT. The illustrations reiterate the impression that relative uptake of 68Ga-DOTATATE/FDG in the NEN lesions forms a valuable parameter for assessing the dynamic tumor biology in continuum and thus personalizing the treatment strategies.

This study aimed at assessing the performance of 177Lu-DOTATATE-based peptide receptor radionuclide therapy (PRRT) in de-differentiated thyroid carcinoma thyroglobulin-elevated negative iodine scintigraphy (TENIS) in terms of clinical efficacy and outcome. This is a retrospective analysis of patients of TENIS who had undergone PRRT in a tertiary care setting. The selected patients were analyzed for the following parameters: (i) the patient characteristics, (ii) the metastatic burden, (iii) study of PRRT cycles and activity, (iv) response assessment (undertaken by three-parameter scale: symptomatic including Karnofsky/Lansky Performance scoring, biochemical and scan features) employing predefined criteria (detailed in methods), and (v) Grade III/IV hematological or renal toxicity. According to the qualitative uptake of the tracer in somatostatin receptor (SSTR)-based imaging (with either 99mTc-HYNIC-TOC/68Ga-DOTATATE), the lesions were divided into the following four categories: Grade 0: no uptake, Grade I: uptake less than the liver but more than background, Grade II: uptake equal to the liver, and Grade III: uptake more than the liver. A total of eight patients of TENIS who had undergone 177Lu-DOTATATE were retrieved. Among those eight patients, the follow-up duration (from the time of the 1st PRRT cycle) at the time of analysis ranged from 7 to 52 months, with an average of 34 months. At the time of assessment, two (25%) out of the eight patients had expired due to extensive metastatic disease and 6 (75%) were alive. On symptomatic response, complete disappearance of symptoms was found in one patient (12.5%), whereas three patients (37.5%) showed partial improvement in symptoms after PRRT and four patients (50%) showed worsening of and appearance of new symptoms. On biochemical response, reduction in serum thyroglobulin (TG) was found in three patients (37.5%) after PRRT and increase in serum TG was noticed in the rest of five patients (62.5%). Imaging response showed stable scan in two patients (25%) and progressive disease (PD) in six patients (75%), following a progression-free survival ranging from 7 to 16 months, when they were considered for tyrosine kinase inhibitors in view of PD. There was no obvious evidence of Grade III/IV hematological or renal toxicity in any of the patients, suggesting that the therapy in this group of patients is well tolerated. In addition, we also observed that most patients of TENIS showed low-grade uptake on SSTR-based imaging (Grade II as per our semi-quantitative scale), with only one patient showing Grade III uptake. 177Lu-DOTATATE PRRT demonstrates modest response in SSTR-positive metastatic TENIS patients: (i) low SSTR expression and tracer avidity, and correspondingly lesser degree of targeting by the therapeutic agent and (ii) the fact that most of the TENIS patients usually have fluorodeoxyglucose (FDG)-avid disease, where high FDG avidity is commensurate with aggressive biology and could be the reason for the relatively less response documented. Larger prospective data need to be accrued in this domain in view of its well tolerability and nonavailability of better efficacious and less toxic treatment at present; however, this needs to be tried in receptor-positive cases with high-grade uptake (Score III/IV) for a definitive conclusion.

Second primary malignancies (SPMs) are known to be associated with neuroendocrine tumors (NETs). The association necessitates a careful assessment of the dual-tracer positron emission tomography–computed tomography (PET-CT) imaging findings to identify these malignancies earlier. Such early diagnosis can provide incremental benefit for screening these SPMs apart from their known applications in the management of NETs. A case of incidentally detected metachronous triple-negative breast carcinoma on dual-tracer PET-CT imaging is presented using 18fluoro-2-deoxy-D-glucose (FDG) and 68Ga-DOTATATE that showed a high uptake on FDG but no uptake on somatostatin receptor-based imaging.

This editorial commentary is an expert summary of “Peptide Receptor Radionuclide Therapy (PRRT),” encompassing the essential fundamentals and salient clinical practice points, deliberated and designed in a point-wise manner with theme-based subheadings. Emphasis has been laid on the topics of practical relevance to the referring oncologists with relevant finer points where necessary. A part of the presented overview has been generated from the authors' own practical experience of more than 3500 successful therapies delivered over the last 9 years at a large tertiary care PRRT setting by the joint efforts of Radiation Medicine Centre (RMC), Bhabha Atomic Research Centre (BARC), and Gastrointestinal services of Tata Memorial Hospital (TMH) at the TMH-RMC premises. While the technical indigenization is beyond the scope of this treatise, we must mention here that India had been one of the frontrunners in this treatment modality, and the PRRT services in this country were developed purely as an indigenous effort right from the production of the radionuclide (177-Lutetium) at the reactor and radiolabeling and production of the radiopharmaceutical (177Lu-DOTATATE) by the radiopharmaceutical scientists at the BARC and RMC; such an endeavor allowed this very specialized therapy to be delivered at a very affordable cost in our setting which could be viewed as a major societal contribution of the atomic energy research in this country.

The aim was to assess the effect of standard fixed-dose protocol of 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in patients with borderline low renal function of one parameter (glomerular filtration rate [GFR], effective renal plasma flow [ERPF] or serum creatinine), that was discordant with the remaining parameters and determine the feasibility of this procedure in this group of patients. Renal toxicity of PRRT is a routine issue or concern for such cases. We compared different renal parameters used for pretherapy assessment in patients with borderline low single parameter at baseline and their potential significance with regards to deterioration of renal function subsequently. A retrospective analysis was performed in patients of metastatic neuroendocrine tumors who received therapeutic 177Lu-DOTATATE (using standard fixed-dose protocol) and had borderline compromised renal parameter values (either of GFR/ERPF/serum creatinine). Filtration fraction (FF) was also estimated in each case and all renal parameters were correlated using kappa statistics. The characteristics of cases showing progressive worsening of renal function in the follow-ups were also studied. A total of 15 patients (11 males, 4 females; age range: 32–75 years) were selected among a population of 450 patients. The follow-up duration ranged from 10 to 48 months and administered cumulative activity ranged 9.9–31.3 GBq (2–5 cycles). Based on the parameter characteristics, the study population was divided into following four groups: (a) patients with reduced GFR and maintained ERPF and normal serum creatinine (n = 3); (b) patients with reduced ERPF with maintained GFR and borderline elevated/normal serum creatinine (n = 3); (c) patients with both reduced GFR and ERPF and maintained serum creatinine (n = 1); (d) patients with compromised single kidney function (n = 5). A total of four patients were found who had normal baseline renal function values but showed progressive worsening in the subsequent period. There was no significant change in renal parameters during the follow-up in both Groups a and c. Two patients of Group b demonstrated well-maintained other renal parameters, whereas in 1 patient, there was the evidence of renal toxicity with gradual fall of GFR and ERPF and progressive increase in serum creatinine level. In patients with compromised single kidney function at baseline (Group d), there was overall maintained normal renal parameters, whereas 3 of 5 (60%) showed the increase of FF of the affected kidney. Interestingly, a compensatory hyperfunction was noted in the contralateral kidney. PRRT with 177Lu-DOTATATE is feasible and can be considered in patients with reduced GFR and with maintained ERPF and normal serum creatinine and also in the presence of single compromised parameter if the other two are normal; however, these patients need critical monitoring.

Debate exists on the disease biology and course of primary large cell neuroendocrine carcinoma (LCNEC) of larynx, being classified as a variant of atypical carcinoid by the World Health Organisation-2005 classification, while literature of its aggressive behavior indicating poorly differentiated neuroendocrine carcinoma (akin to pulmonary LCNEC) exists. The utility of dual tracer positron emission tomography/computed tomography (68Ga-DOTATATE and 18F-fluorodeoxyglucose) in deciphering the dynamic tumor biology and feasibility of peptide receptor radionuclide therapy (PRRT) is illustrated in metastatic LCNEC of epiglottis after disease progression following conventional chemoradiotherapy. Relatively, atypical sites of soft-tissue metastases (subcutaneous tissue of arm, scrotal sac, peritoneum, and lamina of thyroid cartilage) and xiphisternum and disease stabilization following 177Lu-DOTATATE PRRT were other noteworthy unique aspects of this report.

Neuroendocrine tumor (NET) occurring in association with other endocrine syndromes forms a distinct entity. The aim was to assess the therapy response profile of the routine peptide receptor radionuclide therapy (PRRT) in this relatively uncommon but clinically challenging subgroup of patients. A retrospective analysis was undertaken from the case records from those who were treated with 177Lu-DOTATATE for metastatic NET. In addition to assessing the therapeutic efficacy, emphasis was also given to study lesional sites and scan pattern. A total of 5 cases were found: In this series of five cases, four belonged to multiple endocrine neoplasia type 1 (MEN1) syndrome; in these four MEN1 syndrome patients, the primary site of NET was thymic region (n = 1), duodenum (n = 1), and pancreas (n = 2). The fifth case was of Cushing's syndrome with the primary site of NET in the thymus. A good symptomatic response was observed in all MEN1 syndrome cases (100%) and progression of symptoms in the patient with Cushing's syndrome. The biochemical response (assessed by measurement of tumor marker serum chromogranin A) demonstrated very good partial response (defined by more than 75% reduction of tumor marker) in 2 MEN1 cases and Cushing's syndrome, good partial response (25–75% reduction of tumor marker) in the remaining 2 MEN1 cases. Scan wise (assessed by technetium [99mTc]-hydrazinonicotinamide [HYNIC]-tektrotyd [TOC]/68Ga-DOTA-NOC/TATE positron emission tomography-computed tomography [PET-CT] and fluorodeoxyglucose [FDG] PET-CT) partial response was observed in 3 MEN1 cases, stable disease was noted in one MEN1 case and disease progression was noted in the patient with Cushing's syndrome. The change in FDG uptake was found to be an important sensitive scan parameter in the treatment evaluation of NETs compared to somatostatin receptor-based imaging in the cases with low MiB1 index. In our series, good palliative response to 177Lu-DOTA-octreotate (DOTATATE) PRRT was observed in most NET patients associated with MEN1 syndrome without any major hematological or renal toxicity.

This review focuses on the potential of advanced applications of functional molecular imaging in assessing tumor biology and cellular characteristics with emphasis on positron emission tomography (PET) applications with both 18-fluorodeoxyglucose (FDG) and non-FDG tracers. The inherent heterogeneity of cancer cells with their varied cellular biology and metabolic and receptor phenotypic expression in each individual patient and also intra-and inter-lesionally in the same individual mandates for transitioning from a generalized "same-size-fits-all" approach to personalized medicine in oncology. The past two decades have witnessed improvement of oncological imaging through CT, MR imaging, PET, subsequent movement through hybrid or fusion imaging with PET/CT and single-photon emission computerized tomography (SPECT-CT), and now toward the evolving PET/MR imaging. These recent developments have proven invaluable in enhancing oncology care and have the potential to help image the tumor biology at the cellular level, followed by providing a tailored treatment. Molecular imaging, integrated diagnostics or Radiomics, biology-driven interventional radiology and theranostics, all hold immense potential to serve as a guide to give "start and stop" treatment for a patient on an individual basis. This will likely have substantial impact on both treatment costs and outcomes. In this review, we bring forth the current trends in molecular imaging with established techniques (PET/CT), with particular emphasis on newer molecules (such as amino acid metabolism and hypoxia imaging, somatostatin receptor based imaging, and hormone receptor imaging) and further potential for FDG. An introductory discussion on the novel hybrid imaging techniques such as PET/MR is also made to understand the futuristic trends.

This communication presents an update on the current role of positron emission tomography-computed tomography (PET-CT) in the various clinical decision-making steps in lung carcinoma. The modality has been reported to be useful in characterizing solitary pulmonary nodules, improving lung cancer staging, especially for the detection of nodal and metastatic site involvement, guiding therapy, monitoring treatment response, and predicting outcome in non-small cell lung carcinoma (NSCLC). Its role has been more extensively evaluated in NSCLC than small cell lung carcinoma (SCLC). Limitations in FDG PET-CT are encountered in cases of tumor histotypes characterized by low glucose uptake (mucinous forms, bronchioalveolar carcinoma, neuroendocrine tumors), in the assessment of brain metastases (high physiologic 18F-FDG uptake in the brain) and in cases presenting with associated inflammation. The future potentials of newer PET tracers beyond FDG are enumerated. An evolving area is PET-guided assessment of targeted therapy (e.g., EGFR and EGFR tyrosine kinase overexpression) in tumors which have significant potential for drug development.