68Ga-PSMA PET/CT: effect of external cooling on salivary gland uptake / PET/CT com 68Ga-PSMA: efeitos do resfriamento externo na captação pelas glândulas salivares

Abstract Objective: To evaluate the effect that external cooling of the salivary glands (ECSG) has on the uptake of gallium-68-labeled prostate-specific membrane antigen (68Ga-PSMA), as an indirect assessment of the capacity of ECSG to reduce the local dose in lutetium-177-PSMA-617 radioligand therapy. Materials and Methods: Ten patients with prostate cancer were submitted to 68Ga-PSMA positron emission tomography/computed tomography with unilateral ECSG. The ECSG was started at 30 min before the injection of the radiotracer and maintained until the end of image acquisition (1 h after injection). Each salivary gland was assessed by determining the maximum, mean, and peak standardized uptake values (SUVmax, SUVmean, and SUVpeak, respectively). The volume of each gland was determined in a volume of interest delineated by a threshold SUVmax of 10%. Paired Student's t-tests were used in order to compare the results. Results: In terms of the SUV parameters, there were no statistically significant differences between the cooled and contralateral salivary glands. However, the mean volume was 27% lower in the cooled parotid glands than in the contralateral parotid glands (p = 0.004). Conclusion: The use of ECSG does not appear to reduce 68Ga-PSMA uptake by the salivary glands. In addition, there is yet no evidence that ECSG is effective in preventing salivary gland toxicity.

Resumo Objetivo: Avaliar o impacto do resfriamento externo de glândulas salivares (REGS) na captação de 68Ga-PSMA como marcador indireto dessa intervenção para redução da dose local na terapia com 177Lu-PSMA. Materiais e Métodos: Dez pacientes com câncer de próstata foram submetidos a PET/CT com 68Ga-PSMA com REGS unilateral. O resfriamento se iniciou 30 minutos antes da injeção do radiofármaco até o fim da aquisição de imagem, 1 hora após a injeção. Cada glândula foi avaliada para os valores de captação padronizados máximo, médio e pico (SUVmáx, SUVmédio e SUVpico, respectivamente). O volume foi definido por um isocontorno usando 10% do SUVmáx. Os resultados foram comparados com o teste t de Student. Resultados: Não houve diferença estatisticamente significante entre os valores de SUV das glândulas resfriadas e seus controles. Houve 27% de redução volumétrica (p = 0,004) nas parótidas resfriadas em comparação ao controle. Conclusão: Não houve redução da captação de 68Ga-PSMA nas glândulas salivares ao REGS. Atualmente não há evidências que suportem essa prática clínica.

Estimation of renal absorbed doses in the treatment of neuroendocrine tumors using 177Lu-DOTA-TATE / 中华放射医学与防护杂志

Objective:To estimate the renal absorbed dose in the treatment of neuroendocrine tumors using 177Lu-DOTA-TATE and to assess the radiation safety and guide the treatment. Methods:The dosimetric calculations of patients treated with 177Lu-DOTA-TATE were carried out based on planar images of single photon emission computed tomography (SPECT). The regions of interest (ROIs) of the whole body and kidneys were delineated and converted into activity. Accordingly, the time-activity curves of the ROIs were obtained. The effective half-lives and cumulative activity of ROIs were calculated through the fitting of a single exponential equation of the ROIs. Then the absorbed doses were calculated based on the medical internal radiation dosimetry (MIRD) formalism. Results:A total of 11 patients with neuroendocrine tumors received 18 cycles of treatments with 177Lu-DOTA-TATE. The effective half-lives of 177Lu-DOTA-TATE in the whole body and kidneys were 20.0-99.8 h and 38.2-75.2 h, respectively, with an average of (57.3 ± 21.4) h and (53.1 ± 12.5) h, respectively. The renal absorbed doses of 177Lu-DTA-TATE were 0.25-1.48 mGy/MBq, with an average of (0.90 ± 0.31) mGy/MBq. The minimum and maximum renal absorbed doses in a single treatment cycle were 1.8 Gy and 9.6 Gy, respectively, while the maximum renal absorbed dose in multiple treatment cycles was 21.7 Gy. Conclusions:The renal absorbed doses in the treatment of neuroendocrine tumors using 177Lu-DOTA-TATE were estimated. The result indicate that the renal absorbed doses were lower than the tolerable dose limits. This study is expected to guide the precise treatment of neuroendocrine tumors.

Eruption of Metastatic Paraganglioma After Successful Therapy with ¹⁷⁷Lu/⁹⁰Y-DOTATOC and ¹⁷⁷Lu-DOTATATE / 대한핵의학회잡지

Metastatic paraganglioma treatment options are limited. Peptide receptor radionuclide therapy (PRRT) has been introduced as a novel management option for metastatic neuroendocrine tumors demonstrating safety, efficacy, and increased quality of life.We present two cases of marked progression of metastatic paraganglioma following initial partial response to PRRT. Given their positivity on ⁶⁸Ga-DOTATATE PET/CT and ¹¹¹In-octreotide SPECT, they underwent PRRT. Imaging following treatment revealed significant improvement in size and intensity, with some foci nearly completely resolved in one patient, and disease regression with a decrease in the number and size of bone and liver lesions in the second patient.Within months, repeat imaging in both patients revealed extensive metastatic disease with new lesions, which eventually lead to their deaths. The mechanism for rapid disease progression after partial response is not well understood, although it could be related to initially high Ki-67 levels or ¹⁸F-FDG PET/CT SUV(max) values. However, naturally rapid disease progression despite PRRT response cannot be excluded. This finding warrants the importance of proper patient counseling along with early and accurate pre-PRRT assessment, taking into consideration the above potential risk factors for therapy response in order to personalize treatment regimens and achieve maximum patient benefit.

The first application of Ga-68 and Lu-177 theranostics in the Philippines: A rare case of mediastinal small cell neuroendocrine carcinoma

@#A 43-year-old female with a surgically unresectable and non-secretory mediastinal small cell neuroendocrine carcinoma waws previously given the protein kinase inhibitor Everolimus with intolerable nausea and fatigue. High somatostatin receptor expression of the known tumor was seen on 68Ga-DOTATATE PET/CT scan. She was then given 6.4 GBq of 177 Lu-DOTATATE with no adverse events. A follow-up 68Ga-DOTATATE PET/CT scan three months post-treatment showerd stable DOTATATE affinity with no evidence of metastasis. this case presents an overview of peptide receptor radionuclide therapy (PRRT), especially for multidisciplinary teams in the Philippines, as 68Ga and 177 Lu theranostics is introduced in the country.

Estimation of tumour volume at therapy initiation by back-extrapolating the post-therapy regression curve of tumour volume

Background: Tumour volume at therapy initiation, Vi, is rarely available in cancer patients, and the last pre-treatment tumour volume available is from previous diagnostic imaging (Vd). Therapeutic efficacy is thus evaluated by comparing tumour volume after treatment with Vd, instead of Vi, which results in underestimation of treatment efficacy. Vi, together with Vd, can also be used for estimation of the natural growth rate of tumour valuable for, e.g., screening programs, prognostication and individualised treatment planning such as chemotherapy scheduling. The aim of this work was to study the feasibility of estimating Vi by back-extrapolating the post-therapy regression of tumour volume, based on data from animal model. Methods: Nude mice bearing human neuroendocrine GOT1 tumour cell line were treated with 177Lu-DOTA-TATE. Tumour volumes were measured regularly after therapy and Vi was estimated by back-extrapolation of (a) linear and (b) exponential regression lines of the two earliest post-therapy tumour volumes and (c) the long-term exponential regression of tumour volume. The estimated Vi values (Vest) were compared with the measured volume of tumour at therapy initiation. Results: The linear regression of the two earliest post-therapy tumour volumes gave the best estimate for Vi (Vest = 0.91 Vi, p < 0.00001), compared with the exponential regression models either on short-term (Vest = 2.30 Vi, p < 0.01), or long-term (Vest = 0.93 Vi, non-significant) follow up of tumour volume after therapy. Conclusion: Back-extrapolation of the early linear regression of tumour volume after therapy gave the best estimate for tumour volume at time of therapy initiation. This estimate can be used as baseline for treatment efficacy evaluation or for estimation of the natural growth rate of tumour (together with the measured tumour volume at pre-treatment diagnostic imaging)

Incidental Detection of Parathyroid Adenoma on Somatostatin Receptor PET/CT and Incremental Role of ¹⁸F-Fluorocholine PET/CT in MEN1 Syndrome / 대한핵의학회잡지

Multiple endocrine neoplasia type 1 (MEN1) syndrome is characterized by combined occurrence of tumors of endocrine glands including the parathyroid, the pancreatic islet cells, and the anterior pituitary gland. Parathyroid involvement is the most common manifestation and usually the first clinical involvement inMEN1 syndrome, followed by gastroentero-pancreatic neuroendocrine tumors (NETs). Here we present a case where the patient initially presented with metastatic gastric NET and a single parathyroid adenoma was detected incidentally on ⁶⁸Ga-DOTANOC PET/CT done as part of post ¹⁷⁷Lu-DOTATATE therapy (PRRT) follow-up. Further ¹⁸F-fluorocholine PET/CT showed four adenomas for which the patient subsequently underwent subtotal parathyroidectomy.

Terapia con [ 177 Lu - Dota0 - Tyr 3 ]-Octreotate ( 177 Lu-Dotatate) en pacientes con tumores avanzados de origen neuroendocrino: experiencia inicial y resultados preliminares / Therapy with [ 177 Lu - Dota0 - Tyr 3 ]-Octreotate ( 177 Lu-Dotatate) in Patients with Advanced Neuroendocrine Tumors: Initial Experience and Preliminary Results / Terapia com [ 177 Lu - Dota0 - Tyr 3 ]-Octreotate ( 177 Lu-Dotatate) em Pacientes com Tumores Avançados de Origem Neuroendócrino: Experiência Inicial e Resultados Preliminares

Resumen Objetivo: Mostrar la experiencia inicial y los resultados preliminares de la terapia con [177Lu -Dota0 - Tyr3] - Octreotate (177Lu-Dotatate) en pacientes tratados en la Fundación Cardioinfantil - Instituto de Cardiología (FCI-IC) debido a que la experiencia derivada de esta práctica en países latinoamericanos es poco conocida. Materiales y métodos: Se realizó un análisis descriptivo y retrospectivo en pacientes a los que se les realizó terapia con 177Lu-Dotatate con al menos una dosis y un año de seguimiento. Se incluyeron 8 pacientes (4 mujeres y 4 hombres) de edad media: 57 años (50-63). Se administraron 24 dosis en total, 3 dosis en promedio por paciente, 187 GBq totales y 23,5 GBq dosis/paciente. Se valoró la respuesta al tratamiento y la presencia de efectos adversos. Resultados: El tiempo medio de seguimiento fue de 46 meses (26-72 meses). 5/8 pacientes tenían diagnóstico de tumores neuroendocrinos (TNE) de origen pancreático, 2/8 de origen gástrico y 1/8 de yeyuno. 7/8 pacientes tenían compromiso metastásico; 1/8, a pesar de no tener afectación metastásica, fue considerado irresecable. 7/8 pacientes presentaron síntomas posterapia leves y 1/8 eventos adversos serios. 2/8 pacientes tuvieron respuesta parcial, 4/8 enfermedad estable y 2/8 respuesta completa. Sin embargo, al final del seguimiento un paciente que tuvo respuesta completa presentó recaída y otro, respuesta parcial con posterior progresión y muerte. Conclusiones: En la institución, la terapia con 177Lu-Dotatate ha sido segura y eficaz en pacientes con TNE como alternativa terapéutica con adecuados niveles de respuesta y control de la enfermedad con eventos adversos leves, esperables y eventos serios mínimos autolimitados.

Abstract Objective: To Show the initial experience and preliminary results of therapy with [177Lu -Dota0 - Tyr3] - Octreotate (177 Lu-Dotatate) in patients with neuroendocrine tumors (NET) treated in our institution, because the experience gained from this practice in Latin American countries is poorly known. Materials and methods: A descriptive and retrospective analysis in patients who have undergone therapy with 177 Lu-Dotatate with at least one dose and at least one year of follow-up was performed. 8 patients (4 women and 4 men) with a mean age of 57 years (50-63) were included. A total of 24 doses were given, an average of 3 doses per patient. A total of 187 GBq were administered, equivalent to 23.5 GBq / patient. Response to therapy and the presence of adverse short and long term effects were assessed. Results: The average follow-up time was 46 months (26-72 months). 5/8 patients were diagnosed with pancreatic net, 2/8 of gastric origin and 1/8 of small bowel origin. 7/8 patients had metastatic involvement and 1/8 patient despite not having metastasis was considered unresectable. 6/8 patients had mild post-therapy symptoms and 1/8 serious adverse events. 2/8 patients had partial response, 4/8 stable disease and 2/8 had a complete response. At the end of follow-up, however, one patient who had a complete response presented with recurrence and one with partial response showed progression and death. Conclusions: In our experience, therapy with 177 Lu-Dotatate was safe and effective in patients with net as an alternative therapy with appropriate levels of response and disease control and with mild expected adverse events and self-limiting minimum serious events.

Resumo Objetivo: Mostrar a experiência inicial e os resultados preliminares da terapia com [177Lu - Dota0 - Tyr3] -Octreotate (177Lu-Dotatate) em pacientes tratados na nossa instituição, devido a que a experiência derivada desta prática em países latino-americanos é pouco conhecida. Materiais e métodos: Se realizou uma análise descritiva e retrospectiva em pacientes aos que se lhes tem realizado terapia com 177Lu-Dotatate com ao menos uma dose e ao menos um ano de seguimento. Incluíram-se 8 pacientes, idade média de 57 anos (50-63). Administraram-se: 24 doses em total, 3 doses em média por paciente, 187 GBq totais administrados e 23.5 GBq doses/paciente. Valorou-se a resposta ao tratamento e a presença de efeitos adversos. Resultados: O tempo médio de seguimento foi de 45 meses (26-72 meses). 5/8 tinham diagnóstico de TNE de origem pancreática, 2/8 de origem gástrica e 1/8 de jejuno. 7/8 pacientes tinham compromisso metastático e 1/8 paciente apesar de não ter afetação metastática foi considerado irressecável. 6/8 pacientes apresentaram sintomas pós-terapia leves e 1/8 eventos adversos sérios. 2/8 pacientes tiveram resposta parcial, 4/4 doença estável e 2/8 resposta completa. No entanto, no final do seguimento um paciente que teve resposta completa apresentou recaída e outro resposta parcial com posterior progressão e morte. Conclusões: no nosso meio a terapia com 177Lu-Dotatate tem sido segura e eficaz em pacientes com TNE como alternativa terapêutica com adequados níveis de resposta e controle da doença com eventos adversos leves esperáveis e eventos sérios mínimos autolimitados.

Distribution and accumulation of 177Lu-labeled thermally cross-linked superparamagnetic iron oxide nanoparticles in the tissues of ICR mice / 대한수의학회지

To investigate kinetics of free 177Lu and 177Lu-labeled thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION), suspensions were intravenously injected into the tail vein of mice at a dose of 5 microCi/mouse or 15 mg/kg body weight, respectively. Free 177Lu radioactivity levels were highest in kidney followed by liver and lung 1 day post-injection. 177Lu-labeled TCL-SPION radioactivity in liver and spleen was significantly higher compared to that of other organs throughout the experimental period (p < 0.05). Radioactivity in blood, brain, and epididymis rapidly declined until 28 days. Based on these results, TCL-SPION could be a safe carrier of therapeutics.

Tratamento de tumores neuroendócrinos por medicina nuclear: revisão sistemática da eficácia e segurança do radiofármaco Dotatate-177Lu / Treatment of neuroendocrine tumors by nuclear medicine: a systematic review of efficacy and safety of the radiopharmaceutical 177Lu-Dotatate

O DOTATATE-177Lu é um análogo de somatostatina radiomarcado que guia a radioatividade para tumores neuroendócrinos (NETs) que superexpressam receptores de somatostatina (SSTRs), promovendo o seu tratamento por terapia radionuclídica receptor-específica (PRRT). O objetivo deste trabalho foi avaliar a eficácia e a segurança da PRRT dos NETs com o DOTATATE-177Lu, através de uma revisão sistemática da literatura. A PRRT com o DOTATATE-177Lu foi eficaz no tratamento de NETs metastáticos ou inoperáveis que expressam SSTR tipo 2. Observou-se estabilização ou até regressão da doença em 20 a 50 % dos casos. Já a prevalência de remissão total da doença, apesar de numericamente baixa, foi satisfatória, principalmente levando-se em conta o estágio avançado dos tumores. Os efeitos adversos mais comuns da PRRT foram toxicidade renal e hematológica. Apesar dos estudos evidenciarem a eficácia e a segurança da PRRT com o radiofármaco, essa terapia ainda é considerada em desenvolvimento.

The DOTATATE-177Lu is a radiolabeled somatostatin analogue that guides the radioactivity to neuroendocrine tumors (NETs) that overexpress somatostatin receptors (SSTRs), allowing their treatment by receptor- specific radionuclide therapy (PRRT). The aim of this study was to evaluate the efficacy and safety of PRRT of NETs with DOTATATE-177Lu through a systematic literature review. PRRT with 177Lu - DOTATATE was effective in the treatment of inoperable or metastatic NETs that express SSTR type 2. Stabilization or regression of the disease was observed in 20 to 50% of the cases . The prevalence of total remission, although numerically low, was satisfactory, especially taking into account the advanced tumor stage. The most common adverse events in the PRRT were hematological toxicity and renal failure. Despite studies demonstrate the efficacy and safety of PRRT with the radiotracer , this treatment modality is still considered under development.

Estudio biocinético y dosimétrico de un kit de producción local de 177Lu-EDTMP para su uso como agente paliativo del dolor / Biokinetic and dosimetric study of 177Lu-EDTMP in the palliative treatment of skeletal metastasis

Los radiofármacos con afinidad por el tejido óseo como el ácido etilen-diamino-tetrametilen-fosfónico (EDTMP) marcado con radioisótopos emisores beta- han demostrado su eficacia en el tratamiento paliativo de las metástasis óseas. Se realizó un estudio biocinético y dosimétrico del 177Lu-EDTMP en ratones NIH. Los resultados obtenidos fueron extrapolados a humanos. Se estimó la dosis absorbida en órganos para dos modelos: un hombre adulto y una mujer adulta. El 177Lu-EDTMP posee una selectiva captación en hueso, una rápida eliminación en sangre e insignificante captación en tejidos no óseos. La dosis en hueso estimada para el hombre se encuentra entre 14,7-15,3 cGy/mCi y entre 19,6-20,4 cGy/mCi para la mujer. La toxicidad en médula ósea representa el factor limitante de este tipo de terapia, y para evitar superar la dosis máxima que ésta puede tolerar (200 cGy), se encontró que la actividad máxima segura de 177Lu-EDTMP que puede ser inyectada al hombre (73,9Kg), corresponde a un valor de 1,01 mCi/kg y a un valor de 1,25 mCi/Kg para la mujer (56,9Kg).

Bone-seeking radiopharmaceuticals like the ethylenediaminetetramethylene phosphonic acid (EDTMP) labeled with beta--emitting radioisotopes have demonstrated their efficacy in the palliative treatment of skeletal metastasis. A biokinetic and dosimetric study of 177Lu-EDTMP in NIH mice was performed. The results obtained were extrapolated to human. We estimate the absorbed doses in organs for two models: an adult male and an adult female. 177Lu-EDTMP has a selective uptake in bone, a rapid elimination from blood and negligible uptake in non-skeletal tissues. The estimated dose in bone is between 14.7-15.3 cGy/mCi for men and between 19.6-20.4 cGy/mCi for women. Bone marrow toxicity represents the limiting factor in this kind of therapy, and to avoid exceed the maximum dose it can tolerate (200 cGy), it was found that the maximum safe activity of 177Lu-EDTMP to be injected to male (73.9 kg), corresponds to a value of 1.01 mCi/kg and a value of 1.25 mCi/kg for female (56.9 kg).

Tratamiento de tumores neuroendocrinos (TNE) con péptidos análogos de la somatostatina marcados con radionucleidos / Treatment of neuroendocrine tumors (NET) with radiolabelled somatostatin analogues

Propósito. Los TNE avanzados tienen escasa respuesta a radioterapia o quimioterapia, el tratamiento sistémico con análogos de la SST radiactivos es una herramienta promisoria en su tratamiento. Presentamos nuestra experiencia, pionera en Latinoamérica, utilizando análogos de SST marcados con 90Y ó 177Lu. Material. Evaluamos 40 pacientes (50.3 años, rango 12-74) con TNE confirmados histológicamente y sobre-expresión de receptores de SST demostrada mediante imágenes. SPECT (111In-DOTATOC) ó PET/CT (68Ga-DOTATATE). Se evaluó respuesta clínica, laboratorio, imágenes con 111In-DOTATATE, post-terapia con 90Y ó 177Lu, 68Ga-DOTATATE PET/CT o TAC. Resultados. Observamos progresión de enfermedad en 10 (25.0 por ciento), remisión parcial en 25 (62.5 por ciento), enfermedad estable en 3 (7.5 por ciento) y remisión completa en 2 (5.0 por ciento). Hubo escasa toxicidad sin deterioro renal significativo. Observamos reducción tumoral y mejoría de calidad de vida en la mayoría de los pacientes. Conclusión. La terapia con radiopéptidos es un procedimento seguro y efectivo en el tratamiento de TNE avanzados.

Purpose. Advanced NETs have little response to radiotherapy or chemotherapy, systemic treatment with radioactive SST analogous is a promissory tool in its treatment. We present our pioneering experience in Latin America using analogous of SST labeled either with 90Y or 177Lu. Materials. We evaluated 40 patients (50.3 years, range 12-74) with histological proved NET and SST receptors over-expression demonstrated by SPECT or PET/CT images with 111In-DOTATOC or 68Ga-DOTATATE. We evaluated clinical response, laboratory test, images with 111In-DOTATATE, 90Y, 177Lu, and 68Ga-DOTATATE PET/CT or CT. Results. We observed progression of disease in 10 (7,5 percent), partial remission in 25 (62,5 percent), stable disease in 3 (7,5 percent) and complete remission in 2 (5,0 percent). There was little toxicity without significant renal deterioration. We observed tumor mass reduction and improvement of quality of life in most of the patients. Conclusion. The therapy with radiopeptides is a safe and effective procedure in the treatment of advanced NET.